Endocrine Flashcards

Question

Which is isotope used in thyroid

Answer 1

* Tc-99m pertechnetate or I123 = nuclear uptake scan I131 = radioactive iodine

Answer 2

* Substernal goiter – 5 to 24 percent * Neurogenic tumors (eg, ganglioneuromas in the posterior mediastinum) – 20 percent * Thymoma – 18 percent * Bronchogenic and pericardial cysts – 15 percent * Lymphoma – 5 to 10 percent * Teratoma (anterior mediastinum) – 8 percent

Answer 3

* **Definition:** * Chronic autoimmune thyroiditis * “Auto-immune lymphocytic thyroiditis” * Incidence/epidemiology: * Most common cause of hypothyroidism (in iodine sufficient world) * **Aetiology & risk factors:** * F\>M 7:1 * 40-60 years of age * Other autoimmune conditions * Diabetes * Coeliac * Addisons * Pernicious anaemia * Vitiligo * **Pathophysiology:** * Autoimmune-mediated destruction of the thyroid gland involving apoptosis of thyroid epithelial cells * Antithyroid antibodies (anti-TPO, anti-thyroglobulin), infiltrate of the gland by lymphocytes with subsequent fibrosis and scarring * Combination of genetic and environmental factors * Link with Graves Disease * Initial hyperthyroidism followed by hypothyroidism * **Clinical manifestations:** * _Usually asymptomatic_ or hypothyroid symptoms * Gradual thyroid failure with or without (atrophic) goitre * Rarely have a tender goitre, doesn’t cause obstructive symptoms * Usually permanent except in children and post-partum * Signs & symptoms of hypothyroidism * Either due to low metabolic rate OR accumulation of matrix glycosaminoglycans in the interstitial spaces * Dermatological * Cool, pale, coarse dry skin * Brittle nails * Non pitting odema * Vitiligo * Alopecia * Eyes * Periorbital oedema * Haematological * Anaemia – normochromic normocytic * Pernicious anaemia 10% of patients (macrocytosis) * Cardiovascular system * Pericardial effusion * Bradycardia * Worsened heart failure * * **Macroscopic features:** * Local or diffuse process * **Microscopic features:** * Lymphocytic infiltration of the thyroid with follicular destruction, plasma cells, and lymphoid nodules * **Investigations:** * Bloods are diagnostic * Thyroid Function Tests * High TSH * Low free thyroxine (T4) * Auto antibodies * Anti TPO (thyroid peroxidase) and thyroglobulin * FNA if suspicious nodule * **Treatment:** * Non operative/medical * Thyroxine therapy helps to replace T4 but also suppresses TSH secretion and helps reduce inflammation * Levothyroxine (synthetic T4) 100-125mcg/day, but need to monitor TSH 6 weekly until normal and a steady state * Prognosis:

Answer 4

* **Definition:** * Autoimmune cause of hyperthyroidism * **Incidence/epidemiology:** * Most _common_ cause of hyperthyroidism * Other common causes * Toxic multinodular goitre * Toxic adenoma * Early phase of thyroiditis * Drug induced (either thyroxine or iodine containing) * Other uncommon causes * TSH secreting pituitary tumour * Struma ovarii (rare ovarian tumour) * Choriocarcinoma * Factitious * **Aetiology & risk factors:** * Family history * 2-4^th decade of life * Female 4:1 * Hepatitis C on interferon * Stress * Smoking * Post partum * **Pathophysiology:** * Auto antibodies stimulate the TSH receptor signalling growth * Eye disease (cross reactivity) * TSHR antibodies activate fibroblasts, lymphocytes and adipocytes * EOM, connective tissue and fat all increase in volume due to inflammation and acculumation of GAG glycosaminoglycans (mucopolysaccarides deposition) * Cornea loses its protection from the eyelid * **Clinical manifestations:** * “Moderate to severe hyperthyroidism, new opthalmopathy and diffuse goitre” * Signs * Graves ophthalmopathy (20% of patients) * 3 subtypes * Ocular myopathy * Fibrosis of the EOM * Diplopia * Exophthalmos * Congestive ophthalmopathy * Periorbital oedema * Conjunctival injection * Exopthalmos * Chronic eyelid lad * Inability to completely oppose the eye lids * Lag and retraction of the eyelid * Corneal ulceration * Lid retraction * Lid lag * Exophthalmos * Keratopathy * Opthalmoplegia from EOM paralysis * Compressive optic neuropathy * Macroscopic features: * Microscopic features: * **Investigations:** * TFT * High T3-4 and low TSH * Common to have (70%) LFT dysfunction mild * Autoantibodies * Thyroglobulin AB (usually Hashimotos but can be in Graves – note these can effect thyroglobulin monitoring for tumour marker after thyroidectomy) * Thyroid peroxidase (usually Hashimotos but can be in Graves) * Thyrotropin or TSH receptor antibodies (typical in Graves) * USS * Hypervascularity (thyroid inferno on doppler) * Diffuse swelling * Hyperechoic heterogenous echotexture * Radioactive iodine uptake scan (diffuse uptake) * **Treatment:** * Non operative/medical * Graves opthalmopathy * Referral to ophthalmologist – may need eyelid surgery * Return patient to euthyroid status **but not** radioactive iodine * **Smoking cessation** * Corneal lubrication topical * Mild bed head elevation * Glasses during the day to protect from wind/dirt * Night shields for eyes * NSAIDS * Selenium * Steroids * If severe may need IV dexamethasone or plasma phoresies and orbital decompression, radiation treatment to the retroorbital tissues * Symptomatic & definitive * Symptomatic * B blocker (propranolol) or calcium channel blocker * Potassium iodide * Lugol’s iodine [potassium iodide with iodine water] * 10 days, 5-6 drops tds (or potassium iodide 60mg tds) * Definitive * 3 options for Graves Disease * Need to consider pregnancy and Graves opthalmopathy * Antithyroid drugs (ATD) include carbimazole or propylthiouracil * Carbimazole * 5mg tablets, 12-18 months, aim to stop treatment, 50:50 chance of remission * Side effect: * Agranulocytosis (fever, malaise, pharyngitis) * Teratogenic affects * Propylthiouracil (PTU) * Indication: * 1&3^rd trimester * Thyroid storm * If carbimazole is ineffective * Side effect: * Hepatic necrosis * Interferes with the synthesis of thyroxine by inhibiting TPO (coupling of iodine and tyrosine), PTU also inhibits conversion of T4 to T3 * Radioactive iodine * I131 molecule, given as small dose, absorbed into the blood stream from the GI tract, the thyroid is the only tissue in the body that takes up iodine, it is concentrated within the gland, so the radiation is localised to the gland * Can take up to 6 months to work and may need second dose to be effective * Contraindications: * Graves eye disease – can worsen in 15% of patients * Pregnancy or breast feeding for 12 months after treatment * Need radioactive precautions for a few days * Side effects: * Hypothyroidism (80%) * Operative * Total thyroidectomy * Indications * Failed medical therapy * Anatomical reasons (possible cancer or nodules, tracheal compression) * Urgency of treatment – quickest way to return to euthyroid * Contraindications to anti thyroid drugs (major reactions) * Contraindications to RAI (Pregnancy), second trimester pregnancy * Thyroid eye disease * Patient preference * Significant risk of recurrence with subtotal options * Prognosis:

Answer 5

* **Treatment:** * Medications per NG if needed * Glucocorticoids * Potassium Iodide * B blockade * Propranolol * Thioamide * Cholestyramine * Bile-salt sequestrants bind thyroid hormones in the intestine and thereby increase their fecal excretion. * ICU care * Cooling * Empiric antibiotics * Treat underlying thyroid condition; radioactive iodine or thyroidectomy * **Prognosis** * Mortality 20%

Answer 6

* _TIRADS_ (ACR Thyroid Imaging, Reporting and Data System) * 1. Composition * 0 = cystic or spongiform * 1 = mixed (solid & cystic) * 2 = solid (or nearly completely solid) * 2. Echogenicity * 0 = anechoic * 1 = iso/hyperechoic * 2 = hypoechoic * 3 = very hypoechoic * 3. Shape * 0 = wider than tall * 3 = taller than wide * 4. Margin * 0 = smooth/ill defined * 2 = lobulated/irregular * 3 = extrathyroidal extension * 5. Echogenic foci * 0 = none or large comet tail artifact * 1 = macrocalcifications (can be associated with medullary) * 2 = peripheral rim calcification (eggshell, can be seen in malignancy) * 3 = punctate echogenic foci (microcalcifications) (psammoma bodies) * Total * 0 = TIRADS 1 = Benign * 2 = TIRADS 2 = Not suspicious * 3 = TIRADS 3 = Mildly suspicious * 4-6 = TIRADS 4 = Moderately suspicious * 7+ = TIRADS 5 = Highly suspicious * Remember * Cancer is more **_hypo_**echoic (solid component – obviously a hypoechoic cyst is good) * Hyperechoic is good * Intact rim calcification is ok, invasion through rim is bad, internal microcalcification bad

Answer 7

1: Non diagnostic * Need 3+ clusters with 20+ cells in each * 1-4% risk of malignancy 2: Benign * 0-3% risk of malignancy * Should we the most common category * Colloid, hyperplastic adenoma, thyroiditis * Repeat USS 12 months 3: Atypia of undetermined significance, follicular lesion of undetermined significance * 5-15% risk of malignancy (should be a minor of results overall) * Close follow up at 3 months with FNA or if other high risk features maybe repeat sooner or diagnostic hemithyroidectomy 4: Follicular neoplasm or suspicion of follicular neoplasm * 20-30% risk of malignancy * Is there capsular invasion or vascular invasion – can only tell on histology * Typically management is diagnostic hemithyroidectomy 5: Suspicious for malignancy * 60-75% risk of malignancy * Usually papillary thyroid cancer * Nuclear inclusions/grooves, orphan Annie eyes, psammoma bodies * Surgical option depends on size, lateral neck involvement 6: Malignant * 97-99% risk of malignancy

Answer 8

Female more common (but also nodules more common) Age * Red flags for cancer (Win Meyer Rochow) * Male * Extremes of age (\<20 or \>50 years) * Symptoms local invasion (dysphagia, hoarseness) * Radiation to the H&N or background radiation * Familial cancer Ionizing radiation Dietary iodine deficiency (follicular) Previous long term thyroid inflammation (Hashimotos) Family history * Thyroid cancer * Medullary cancer (20%) MEN 2A and 2B *RET* * FAP *APC* * Cowdens *PTEN* (uterine, breast, hamartomas) * Carney complex type one (benign adrenal adenomas) * Thyroid cancers of any types (genes not yet recognized yet)

Answer 9

* Differentiated * 85% papillary, 10% follicular * Arise from follicular thyroid/epithelial cells * Produce thyroglobulin * _Take up iodine_ * Differentiated have low mutation rate – usually one particular driver mutation Papillary * Spread via * Lymphatic (30%) * Extra thyroid direct extension * 1% Lung most common distant metastasis followed by bone * Genetic mutations * BRAF (2/3s), RAS, RET/PTC most common * Poorly differentiated ones have acquired a further TERT or Tp53 mutation Follicular * Spread via * Haematogenous; dissemination to lung, bone, liver * Genetic mutations * RAS * Pi3K * PTEN * PAX8

Answer 10

* De-differentiated * 1-5% * Anaplastic (arise from follicular cells) * De novo or de differentiation of well differentiated cancer * Invasive of local vessels and RLN nerve * Early metastasis to lung, bone and brain Medullary * 5% * C cells – parafollicular * _Don’t take up iodine_ * Neuroendocrine tumour – neuroectodermal origin * Produces calcitonin * RET oncogene mutation = 25% familial and 75% sporadic – associated MEN2A/B * Tubercle of Zuckerkandel most common site? * Spread via * Lymphatics * Metastasis to lymphatics, liver, bone, brain, adrenals Hurthle cell * 5% * Similar in some ways to differentiated * But doesn’t take up iodine as much * Spread * Lymphatic Lymphoma * Rare * Arise from the thyroid stroma Metastasis **to** the thyroid * Renal cell (48.1 %) * Colorectal (10.4 %) * Lung (8.3 %) * Breast cancer (7.8 %) * Sarcomas (4.0 %) * Melanoma (rare)

Answer 11

Papillary * Most found incidentally * Dysphagia or stridor due to mass effect * Hoarseness direct invasion RLN * Lymph adenopathy 30% _Lymph node metastasis_ common *[papillary more common than follicular, thus remember that it has the more common modality of metastasis]* Follicular * Slow growing mass * Regional lymph nodes rarely involved Anaplastic * Rapid neck swelling * Local compression or invasive symptoms Medullary * Diarrhoea * Vasoactive * Neck mass

Answer 12

* No orphan annie (papillary) * Extracapsular or vascular invasion (carcinoma) * Uniform follicles * Subtypes * Can be minimally to widely invasive * Minimally = solid tumour with thick capsule and some invasion * Widely = Infiltration of the capsule and adjacent thyroid tissue and blood vessels * Hurthle cell tumour, encapsulated tumour containing \>75% oncocytic cells which are pink granular eosinophilia cells due to high amount of mitochondria, can be benign or malignant (1/3) with increasing risk with size (\>3cm) and age, can spread lymphatically

Answer 13

* 10+ histological subtypes * Microcarcinoma – indolent (\<1cm than size, usually incidental, usually hemithyroidectomy is enough) * Encapsulated variant, but with local invasion * Infiltrated subtype, sometimes mistaken for Hashimotos * Follicular variant * Insular Poor differentiated poor prognosis * Orphan Annie eye nuclei – dispersed chromatin & **p**ale nuclei, nuclear groove * Branching **p**apillae, fibrovascular stalk * **P**sammaoma bodies – calcified structures in the core of the papillae

Answer 14

* Large amounts of amyloid (homogenous extracellular material) from the calcitonin molecules – congo red * Stain for chromogranin, calcitonin an CEA, wont stain for thyroglobulin * Single discohesive cancer cells

Answer 15

Labs * Calcitonin and CEA for medullary (not thyroglobulin) * TSH * Phaeochromocytoma work up for medullary, prior to surgery * If family history of cancers, or sudden unexplained death * Plasma metanephrines * Calcium, PTH and Vitamin D levels (due to MEN2A hyperparathyroidism) * Refer for RET mutation testing CT * Indications: * Extensive lymphadenopathy * Suggestion of extra thyroid infiltration/invasion * Contrast * Iodine based contrast is OK, it washouts out in a few weeks USS (ATA) + FNA – Bethesda classification (as above) * Papillary * Can be diagnosed on FNA * Follicular * Can’t be distinguished from adenomas on FNA * Anaplastic * Need to exclude another rapid growing mass such as lymphoma Nuclear * Differentiated * Tc99 * I123 (I131 is radioactive treatment) * DOTATE PET * Medullary * Undifferentiated * FDG * 60% risk of malignancy if PET avid

Answer 16

**Active surveillance** * Indication * Micropapillary (\<1cm) * No aggressive disease (high grade), distant disease or lymph nodes * Not located adjacent the RLN or trachea * High surgical risk due to comorbidities * Short life expectancy **Radioactive iodine** * Differentiated cancers only * Need to have high TSH when being given so that it is taken up – give artificial TSH called thyrogen, or stop thyroxine beforehand * Take a stimulated thyroglobulin level at the time of the ablation, also post treatment uptake scan done to check for residual tissue * Contraindications * Pregnancy and breastfeeding 12 months * Side effects * Salivary gland dysfunction, dry mouth or inflammation of the glands * 2 indications: * Adjuvant to improve disease free survival for those without known residual disease * Treatment for residual or recurrent disease (previous total thyroidectomy) * Adjuvant treatment depends on risk stratification (2009 not 2015 which has continuum) * Low * Small * Unifocal * No/minimal nodal disease * 1 month post operative thyroglobulin \<1 * Intermediate * Aggressive histology (extrathyroidal invasion) * Vascular invasion * Nodal involvement * 1 month post operative thyroglobulin 1-10 * High * Gross extrathyroidal extension * R1 resection * +4cm * Extensive vascular invasion * Large lymph nodes \>3cm or extranodal extension * Distant metastatic disease * 1 month post-operative thyroglobulin \>10 **Thyroid suppression with thyroxine** * Differentiated cancers express TSH receptor, by suppressing TSH then decreased risk of recurrence * Give a dose of thyroxine that keeps TSH at \<0.1 in high risk patients, 0.1-0.5 for intermediate patients * Indications * High risk and intermediate risk patients based on ATA guidelines (see above in RAI) * Complications * Arrythmias particularly AF * Osteoporosis * Due to complications need to adjust based on response to treatment after 5-10 years of treatment * 3 risk differing groups: * If suppressed thyroglobulin or negative uptake scan * If negative uptake scan but TG not \<0.1 * If residual disease on uptake scan * Monitoring with serum thyroglobulin, clinical examination, USS/PET/CT * Radioactive iodine resistant disease *  tyrosine kinase inhibitors (Lenvatinib- multiple targets VEGF + RET) * Medullary metastatic disease * Vandetanib and cabozanixib * Anaplastic * Radiotherapy

Answer 17

Condensed version of management * Differentiated = N status, then T status, then high risk features * Medullary = N status and calcitonin levels * Anaplastic = depends on PET scan, minimally morbid resectability and BRAF Lobectomy * Indications * Micropapillary cancer if not for active surveillance * Follicular neoplasm ?adenoma * T1-2 differentiated cancer if no high risk features * WMR lecture, his cut off is T1 (i.e.\<2cm); note iflobectomy 1. Might have multifocal disease 2. Residual thyroid will take up RAI if given 3. Make thyroglobulin surveillance difficult Total thyroidectomy * Straight up for * T2 or N1 * Prophylactic in * High risk features * Radiation exposure as a child or H&N radiation * Family history * Posterior or adjacent the trachea * Aggressive cytology * Extra thyroid spread * Multifocal * Completion TT * Just under half of lobectomy will need TT * R1 resection, local extension, vascular invasion, \>4cm * Higher risk of RLN injury, hypocalcaemia Lymph node management * Generally leave lymph nodes alone unless high risk (prophylactic/prognostic) or involved (therapeutic) * High risk * Same as above * \>4cm or invading surrounding structures * Benefits of prophylactic CND * Improved accurate staging * May indicate RAI if involved * Not much increase in the morbidity compared to TT alone * Reduce the need for re-operative surgery * Lower the post operative thyroglobulin levels * Against prophylactic CND * Most are micrometastatic – unclear survival benefit * No level 1 evidence * RAI is being used less, but upstaging might be unnecessarily be causing us to over treat * Central compartment lymph node dissection - prophylactic * Comprehensive compartment orientated removal of the prelaryngeal, pretracheal and paratracheal lymph node basin * All fat from between the carotid sheaths, level VI * Complications * RLN injury * Hypocalcaemia and hypoparathyroidism * Lateral compartment lymph node dissection * Remove involved compartment and adjacent station nodes, plus central compartment * Special considerations in anaplastic cancer

Answer 18

T * T1 \<2cm * T1a \<1cm * T1b 1-2cm * T2 2-4cm * T3 \>4cm or into strap muscles * T3a \>4cm but limited to thyroid * T3b into strap muscles (any size) * T4 into surrounding tissues beyond strap muscles * T4a invasion into surround tissues including RLNx * T4b invasion into prevertebral fascia, carotid, mediastinal vessels N * N1a Level VI orVII * N1b I-V or retropharyngeal Differentiated AJCC 8^th edition staging * Because the prognosis is so good for young people the staging is age based * \<55 TxNxM0 = stage 1, TxNxM1 = stage 2 * \>55 * Stage 1: T1-2N0M0 * Stage 2: T1-3 **N1** * Stage 3: **T4a** NxM0 * Stage 4a: **T4b** NxM0 * Stage 4b: TxNx **M1**

Answer 19

Exclude phaeo with serum metanephrines They will get a total thyroidectomy Lymphadenectomy depends on calcitonin levels and staging

Answer 20

Cross sectional imaging including FDG PET CT Bronchoscopy and endoscopy for aerodigestive involvement MDT review with Pall care ?Resectable with minimal morbidity? If not then BRAF testing for darafenib If wild type then consider RTx or palliative chemo

Answer 21

* Differentiated * Post operative appointment (wound, TFT, Thyroglobulin 6-8 weeks post op) * 6 month assessment (TSH, T4, TG and TG antibody levels) * 1 year, repeat blood tests and thyroid & neck ultrasound + clinical examination to detect any recurrence or nodal disease – FNA and TG washings of the node * If TG or TG antibodies rising then do ultrasound, if US normal then need whole body RAI uptake scan or PET scan * Medullary * Monitoring calcitonin and CEA levels, ultrasound of the neck and cervical LNs * If calcitonin low – monitor * If calcitonin rising or doubles in \<6 months * USS neck * CT neck, chest, abdo, pelvis * PET scan * Recurrence (differentiated) * Local, lymph nodes or distant disease * Need biopsy to confirm the diagnosis * Staging * RAI scan or PET scan * Local nodal disease * Compartment resection * Distant * Multimodality * Surgery * RAI * Targeted RTx * Thermal ablation * Targeted therapies * Tyrosine kinase inhibitors for radioactive resistant disease * Systemic chemotherapy not traditionally used due to poor response * Can still have good prognosis * Age * Number and distribution of lesions

Answer 22

* **Definition:** * Lymphocyte malignancy involving the thyroid gland * **Incidence** * Accounts for 1-5% of all thyroid neoplasms * Elderly females * Previous Hashimotos thyroiditis * **Classification & Aetiology** * May arise as part of a generalized lymphoma * May develop in pts with chronic lymphocytic thyroiditis (Hashimotos’s) * **Pathogenesis** * “Pseudocystic” mass * Most are non-Hodgkin’s B cell type, diffuse large B cell, marginal zone lymphoma or mixed type * **Clinical Manifestation** * May present with a **_rapidly_** (day on day – inpatient work up) enlarging mass +/- stridor / dysphagia * **Investigation** * FNA +/- core biopsy / open Bx – if Dx unclear from FNA * stage with LDH, CT, BM aspirate * Staging * 1: just within the thyroid * 2: thyroid and regional lymph nodes * 3: both sides of the diaphragm * 4: disseminated * **Management** * [WMR lecture; admit as inpatient, if airway threatened then intubate, get biopsy, treat with chemo] * R CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), plus the monoclonal antibody rituximab (Rituxan) * Surgery used to alleviate Sx of obstruction, or for pts who don’t respond * ?if confined to the thyroid alone, can be treated with lobectomy with subsequent * chemo-radiation (otherwise chemo-radiation alone) * but NB Surgery + chemorads vs chemorads alone = same survival stage for stage * **Prognosis:** * Overall 5-yr survival ≈50% * Pts with extrathryoidal disease have lower survival rates

Answer 23

Numbness and tingling in distal extremities and perioral, tongue Chvostek sign * Tap over the facial nerve  muscle contraction Trousseau sign * BP cuff to inflate the cuff above systolic  after a few minutes carpopedal spasm (tetany of the wrist and fingers) Tetany and trismus Laryngospasm Arrythmias, QTc prolongation Chest pain Seizures

Answer 24

Post operative calcium, PTH and ECG if symptomatic Depends if * Symptomatic * PTH level then Ca2+ level Asymptomatic * PTH \>2.0 * Ca \>2.1 * No action * Ca \<2.1 * Calcitabs (500mg) PO x2 TDS * Repeat bloods within 5 days * PTH \<2 * Ca \>2.1 * Calcitabs (500mg) PO x1 TDS * Calcitriol (0.5mcg) PO 1x daily * Repeat bloods within 5 days * Ca \<2.1 * Calcitabs (500mg) PO x2 TDS * Calcitriol (0.5mcg) PO x2 daily * Remain inpatient Symptomatic * Mild-moderate * Caltrate 1-2 tablets PRN 30 minutes x2 then seek help * Calcitriol to increase the GIT ability to absorb the calcium (can normally only absorb 5 tablets) * Severe * IV replacement * Calcium gluconate (10ml 10% = 2.2mmol calcium) * Bolus 20mL calcium gluconate 10% (4.4mmol) in 100ml NS over 20 minutes * Infusion 100mL calcium gluconate 10% (22mmol) with 900mL NS at 50ml/hr (1.1mmol an hour) * Extravasation causes severe tissue necrosis * Blood test every 3 hours * Monitored bed The main difference between cholecalciferol and calcitriol is that **cholecalciferol is a type of vitamin D that is made by the skin when exposed to sunlight whereas calcitriol is the active form of vitamin D that occurs in the kidney**

Answer 25

* A condition whereby there is parathyroid overproduction * Can be classified as primary, secondary or tertiary * _Primary_ hyperparathyroidism: the autonomous, spontaneous overproduction of PTH * 85% adenoma [single or multiple] * 15% hyperplasia [all abnormal in secondary, more likely hyperplasia in familial] * \<1% carcinoma * _Secondary_ hyperparathyroidism: overactivity of the PTH glands due to hyperplasia in response to a chronic depression in serum calcium (seen in chronic renal failure and vitamin D deficiency) * _Tertiary_ hyperparathyroidism: autonomous overproduction of PTH as a progression of secondary hyperplasia despite normalisation of renal failure * _Don’t mention [Quaternary_: Once the underlying problem has been resolved but hyperparathyroidism persists (despite surgery renal transplant)- note sometimes tertiary/quaternary lumped together]

Answer 26

* Primary hyperparathryoidism * Adenoma 85% * Sporadic * The somatic PRAD1 rearrangement upregulates cyclin D1 in sporadic adenomas * MEN1 * MEN1 gene (chromosome 11q13) * Tumour suppressor gene, codes for menin * Multiglandular, ectopic, and supernumerary disease * Hyperplasia 10% (2+ gland) * MEN2A [not B] * RET mutation (chromosome 10q11.2) * Protooncogene * Carcinoma \<1% * RET protooncogene * CDC73 tumour suppressor gene * Secondary * Multiple asymmetrical gland hyperplasia * 1. Renal Disease * Hypocalcaemia due to reduced reabsorption of urinary calcium * Decreased phosphate excretion→high phosphate * Loss of renal parenchyma→reduced alpha 1 hydroxylase→ decreased activated vitamin D→ reduced intestinal absorption of calcium * 2. Malabsorption * 3. Vitamin D deficiency * 4. Lithium use Parathyroid cancer * Sporadic * Neck radiation * Gene mutation (CDC 73) * RET * Hyperparathyroidism Jaw Tumour Syndrome (HPT JT) * Tumour suppressor gene * Associated with mandible/maxilla tumours, uterine and renal cancer

Answer 27

Primary hyperparathyroidism * Incidental * Hypercalcemia * Bones: Osteoporosis/fractures, bone pain * Stones: Renal stones * Groans: Depression * Moans: Pancreatitis; constipation * Neck lump * Renal * Nephrocalcinosis * Calciphylaxis * Renal impairment * Osteitis fibrosa cystica * Other * Multiple adenomas: pituitary, pancreas, adrenals, thyroid * Limbus keratopathy * Increased joint flexibility * Strong nails and pseudoclubbing * Absence of lamina dura * Calcium deposition in bloods vessels, HTN, heart failure Parathyroid cancer * Nearly always functioning * Extremes of hypercalcaemia * Very high PTH * Neck lump * Hoarse voice (RLN)

Answer 28

* **Macroscopic features:** * Adenoma (usually single) * ovoid, soft, reddish brown tumours, usually a little darker than the normal gland * Carcinoma * Gray white irregular mass sometimes \>10g \>2cm * **Microscopic features:** * Hyperplasia: increased number of chief cells, cells with more abundant, clear cytoplasm “water-clear cells” in a diffuse or multinodular arrangement, decreased fat cells/fat depleted * Adenoma: * Fairly uniformed polygonal chief cells with small, centrally placed nuclei. * A few nests of larger oxyphil cells. * Rim of compressed normal tissue. * Common to find pleomorphic nuclei * Lack of fat * Carcinoma * Uniform and resemble somewhat normal parathyroid cells * Nuclear atypia should not be the defining feature as you can see this in adenomas * Cells form nodular or trabecular pattern with a dense fibrous capsule, invasion of surrounding structures * Parafibromin staining (as 70% are related to parafibromin)

Answer 29

* Concepts * The work-up of parathyroid hyperparathyroidism (like any endocrine surgical condition) depends on **confirming the biochemical abnormality** and then performing imaging studies to **localize the tumour** * Also, need to work up the thyroid gland lesions because you will come across them in the procedure * Exclude 3 mimic conditions and concurrent phaeo: * FHH (familial hypocalciuria hypercalcaemia) * Parathyroid related hormone (small cell or other cancer – paraneoplastic syndrome) * Lytic bone lesions * History * Symptoms of hypercalcaemia or local symptoms * Symptoms of underlying malignancy * Symptoms of endocrine disorder * Medications * Lithium * Thiazides * Vitamin D * Family history * Familial hypocaliuric hypercalcaemia * Endocrine diseases * Previous neck surgery * Previous H&N radiotherapy * Exam * General * Body habitus * Voice * Thyrotoxicosis? * Neck * Masses * Scar * LNs * Bloods * 1. Intact PTH (low = other cancer)(high or inappropriately normal will be PHPT) * 2. PTHrp? * 3. Vitamin D * Serum calcium (+/- ionized calcium) * Serum albumin * Creatinine, urea * Phosphate and magnesium * Expect low serum phosphate unless renal failure * Secreting phosphorus and absorbing chloride (anion exchange) * Serum metanephrines to exclude a phaechromocytoma that can occur in conjugation with hyperparathyroidism in patients with multiple endocrine neoplasia 1 and 2A * 24 hour urinary calcium with calcium/creatinine ratio * Consider Familial hypocalcuric hypercalcaemia * Autosomal dominant – abnormalities in the calcium sensing receptor (CASR) gene * Abnormal calcium-sensing receptors expressed on parathyroid and renal cells  reduced sensitivity to calcium levels  mild hypercalcemia with normal/slightly elevated PTH levels + normal phosphate levels * A urinary calcium level is normal/elevated in patients with PHPT but low/low normal in those with FHH * Patients with FHH will not benefit from surgical intervention * Excluded by measuring the 24hr urinary calcium/creatinine ratio (\<0.01) * Renal failure * Imaging: * Localisation & complications * Detect complications of pHPT * Abdominal imaging for asymptomatic patients (as nephrocalcinosis is an indication for surgery) * DEXA * Secondary hyperparathyroidism  patients with secondary HPT do not undergo localisation studies as they will always have a 4-gland bilateral exploration of their neck * 99mTc Sestamibi scan (early & delayed) and high resolution ultrasound (If these scans are concordant, then removing the identified gland will lead to a cure in 95-98% of patients), 4D CT third line, 4 gland exploration next up * Modalities * Non invasive * USS Neck and renal tract\* * 80% sensitivity * Parathyroids are posterior to the thyroid gland, homogenous, hypoechoic and white hyperechoic rim, hypervascular with a solitary pedicle * Also look at thyroid for nodules that need management at same time * Stones and calcinephrosis * Multiphase CT (4D) * Tripe phase (Non-con, arterial, delayed) * The 4^th dimension is time.. which is stupid because all multiphase scans have time as a 4^th dimension * Thin slices through the neck * Adenoma * Hyperenhancing on the arterial and washed out in the delayed in comparison to the thyroid * MRI * MRI is infrequently utilised in initial workup because of lower spatial resolution and artifacts. Adenomas can show variable signal intensity on MRI. Reported signal characteristics * **T1** * typically intermediate to low signal * subacute haemorrhage can cause high signal intensity * fibrosis or old haemorrhage can cause low signal intensity * **T2** * typically hyperintense * subacute haemorrhage can cause high signal intensity * fibrosis or old haemorrhage can cause low signal intensity * Since most lesions demonstrate high T2 signal intensity, the addition of contrast for MRI does not significantly increase detection. * SPECT * Single Proton Emission Computerized Tomography = Sestamibi-single photon emission computed tomography (SPECT or MIBI-SPECT) combined sestamibi and low dose CT, resolution not as good as a CT normally * Sestamibi\* * Nuclear medicine scan * Radioisotope _technetium-99m_ bound to six (sesta=6) methoxyisobutylisonitrile (MIBI) ligands (as opposed to Tc99 bound to sulphur colloid used in SLNBx) * Taken up by both thyroid and parathyroid, but retained for longer in the parathyroid gland * A second image is obtained after a washout time (approximately 2 hours), and mitochondria in the oxyphil cells of the abnormal glands retaining the 99mTc are seen with the gamma camera * Invasive * Selective angiography * ITA blush * Risky * Selective venous sampling * Comparing the iliac vein PTH to various neck veins (STV, ITV, thymic vein, vertebral vein) * Intraoperative * USS * Methylene blue localization * Gamma probe localisation * Tc-99 m sestamibi isotope on the day of surgery * Containing more than 20% of background radioactivity in a patient with a positive sestamibi scan is consistent with the finding of a solitary parathyroid adenoma * Intraoperative parathyroid levels * Drop of more than 50% after 10 minutes and into the normal range * Is this a MEN problem (1 or 2A, not 2B)? * Genetic counseling should be performed for _patients younger than 40 years_ with pHPT and _multigland disease (MGD)_ and considered for those with a family history or syndromic manifestations

Answer 30

* Depends on severity and underlying cause * Mild * No treatment needed * Oral hydration * Treat underlying cause * Avoid * Thiazides/lithium * Prolonged bed rest * Vitamin D supplements * High calcium diet * \>3.5 or symptomatic * Rehydration 300ml/hr normal saline for a litre then 100ml hour * IV bisphosphonate * Calcitonin * Steroids in granulomatous disease, sarcoid, lymphoma * Dialysis * Calcimimetic (cinacalcet)

Answer 31

Everyone except; * Another cause i.e. FHH, vitamin D deficiency * Those not fit for surgery * Asymptomatic with no end organ effects with either * Life expectancy \<10 years, or * Normal calcium (can offer parathyroidectomy) particularly if lives remotely or age \<50

Answer 32

* After either parathyroidectomy OR thyroidectomy for graves * Strict protocol requiring calcium infusions * High bone turnover during secondary hyperparathyroidism, but when the PTH levels drop the turnover stops and suddenly the bone sucks up magnesium, calcium and phosphate * Symptoms * Severe hypocalcaemia * Hypophosphatemia * Hypomagnesaemia * IV calcium, magnesium replacement

Answer 33

* Identify and remove abnormal parathyroid * Superior Parathyroid * Most upper PT are posterior to upper pole (The 3 landmarks to aid location are): * Inferior cornu of the thyroid cartilage * RLN * The most cranial branch of the inferior thyroid artery * Posterior to thyroid at junction of upper 1/3 & lower 2/3 * Abnormal P IV glands tend to migrate posteroinferiorly, beside or behind the oesophagus * Location of the inferior thyroid vascular pedicle and gentle traction can aid localisation * If not found inspect the perithyroid visceral sheath, particularly the posterior aspect of the upper pole and thyroid capsule. * Identify and preserve the inferior thyroid vessels and RLN. * If still not found move on, search for P III. * Inferior parathyroid * Most lower PT are anterior & inferior to thyroid pole ie. RLN & ITA * Rarely posterior, the more inferior the more anterior they tend to lie. * There is symmetry of position in 60% of cases. * Search from the inferior thyroid artery to the inferior thyroid pole * Often they are found within the thymic sheath (may need to incise or mobilise the thymus) * Carotid sheath * Undescended – look high * If a gland is not found search for it should be abandoned in case a normal gland is devascularised. Move to the other side. * When to stop looking * STOP = when found **_one abnormal gland**_ + _**another 2 look normal_** * 50% drop in PTH intraoperatively @ 10 minutes * When to go hunting * Exploration should be pursued in 3 circumstances: * \<4 found and none are pathological (a likely adenoma remains to be found). * If \<4 glands found and at least 2 are pathological (multiglandular disease, likely others affected). * All four glands found and none are pathological (ectopic supernumerary gland).

Answer 34

* **Definition:** * The adrenals are paired glands that lie on top of the kidneys bilaterally * Composed of two quite different components embryologically and functionally * The outer cortex - derived from the intermediate mesoderm - acts as an endocrine organ producing corticosteroids & androgens * The inner medulla – derived from the ectodermal neural crest – acts as part of the autonomic nervous system producing catecholamines & dopamine (think pituitary – anterior/posterior) * **Embryology:** * Cortex is derived in situ from the intermediate mesoderm along with the gonads and kidney * Medulla is derived by migration of cells from the neural crest and is ectodermal in origin * Adrenals at birth are large but regress as cortex shrinks, * **Surface anatomy:** * Just lateral to the vertebrae with the 12^th rib overlying the inferior portion * **Surrounding structures and relations:** * Within Gretoas fascia but have their own capsule * Left * Short fat crescentric * Overlying the left renal hilum on the medial aspect of the kidney * Medial: aorta * Posterior: lies on the left crus of the diaphragm and front of left kidney (same as right) * Anterior: * Superior part has the lesser sac and stomach bed * Inferior part has the body of the pancreas and the splenic vessels * Right * Tall skinny triangular * Surmounts the right kidney (not enough room to be medial due to the proximity of the IVC) * Posterior: lies on the right crus of diaphragm and the front of the right kidney * Medial: IVC * Anterior: * Bare area of the liver * Below the liver it is covered by the peritoneum of the hepatorenal (Morrisons) pouch * **Arterial supply:** * 3x * Inferior phrenic * Aorta * Adrenal (off renal) * **Venous drainage:** * Single vein * Right is only a few millimietres and direct into the IVC * Left is longer and enters the left renal vein * The cortex drains through the medulla, important as glucocorticoid hormones (from cortex) activate PNMT a medullary enzyme involved in catecholamine synthesis * **Innervation:** * Cortical control is not neural but by ACTH from the anterior pituitary * Medulla - myelinated preganglionic sympathetic fibres from the **splanchnic nerves via the coeliac plexus (T5-9), the fibres synapse directly with medullary cells** * **Lymphatics:** * Para aortic * **Structure within the organ and cell types:** * Contained within Greotas fascia but with some fat and connective tissue separating it from the kidney * The adrenal gland has an outer yellow cortex completely enclosing a much thinner grey medulla * Cortex * Products (salt, sugar, sex – the deeper you go the sweeter it gets) * Aldosterone * Cortisol * Androgens * Three layers or zones (GFR) * Zona glomerulosa (with small columnar cells, minimal cytoplasm, clusters of cells) * Zona fasciculata (largest layer, parallel rows of pale-staining vacuolated cells) * Zona reticularis (a network of smaller, branching cords and darker-staining cells). * Medulla (15% of volume) * Vascular spaces and eosinophilic phaeochromocytes - larger cells * Products * Catecholamines adrenaline (epinephrine) (80%) and noradrenaline (norepinephrine) (20%) * Dopamine * Many of the medullary cells exhibit the chromaffin reaction: they contain fine cytoplasmic granules (the catecholamine precursors) which are coloured brown by chromium salts (hence chromaffin cells) * **Relevance to operations:**

Answer 35

* Benign vs Malignant (primary vs secondary) * Functional vs non-functional * Sporadic vs hereditary

Answer 36

* **Investigations:** * Is it malignant? is it functional? * History * Past medical history of malignant disease * Family history of endocrine disease * Previous imaging that can be compared to * Symptoms * Malignancy * Weight loss * Mass * Acute pain (from haemorrhage) * Back pain * Functional * Cushing’s * Easy bruising * Fatigue * Weight gain * Leg swelling * Mood swings * Mental fogginess * Primary aldosteronism * Muscle cramps * Weakness * Paraesthesia * Sex hormone excess * Infertility * Phaechromocytoma * Episodic spells of dizziness * Palpitations * Headache * Diaphoresis * Tremor * Anxiety * Examination * Signs of hormone excess such as * Cushings * Moon face * Weight gain with buffalo hump * Central obesity and thin extremites * Skin changes (thin with easy bruising, acne, purple striations) * High BP * Abnormal hair growth * New diabetes * Osteoporosis * Proximal myopathy * Cessation of menses * Breast and impotence in men * Primary hyperaldosteronism * Resistant hypertension * Hypokalaemia * Acidosis * Hypernatremia * Sex hormone excess * Hirsutism * Acne * Gynaecomastia * Male pattern baldness * Phaeochromocytoma * Hypertension * Orthostatic hypotension * Retinopathy * Congestive cardiac failure * High BGL * Biochemistry * Cushings (glucocorticoid excess) * Screening: * Low-dose (1 mg) overnight dexamethasone suppression test and midnight salivary cortisol may be required to confirm or exclude * Confirmatory: * 24-hour urinary free cortisol * ACTH level (independent vs dependent) * If high ACTH then do high dose dexamethasone * High dose (8mg) dexamethasone suppression test, if elevated at 8AM then ectopic production (not pituitary) of ACTH * Conn’s (mineralocorticoid excess) * Hypertensive patients with elevated _plasma aldosterone:renin activity ratio_ \>20 * Hypokalaemia is present in only half the patients with primary hyperaldosteronism * Sex hormone * Serum DHEAS and 17-hydroxyprogesterone are measured to exclude adrenal androgen hypersecretion that occurs in some adrenocortical carcinomas or, when bilateral adrenal masses are present, congenital adrenal hyperplasia. * Serum metanephrines * Imaging localisation * CT (thin slices) * Lipid rich low density/attenuation masses on unenhanced CT (\<10 hounsfield units) * Rapid washout of contrasts (\<50% at 10 minutes, \<60% at 15 minutes) * Homogenous with regular outline, rounded, no extension into surrounding structures * \<4cm in size have low malignant risk * MRI * Homogenous enhancement after gadolinium MRI is characteristic * PET * Low fluorodeoxyglucose uptake * Invasive * Biopsy * Unhelpful at differentiating between adenoma and carcinoma and may precipitate a phaeochromocytoma crisis * Maybe for metastatic disease * Selective Venous sampling * Unilateral microadenoma vs bilateral hyperplasia * **Treatment:** * Non operative (\<2% of **_\<4cm_** lesions suspected will harbour carcinoma) * If benign appearing then repeat imaging in 6-12 months plus repeat functional studies * Benign cyst or myelolipoma convincingly diagnosed on imaging, can observe despite size \>4cm * Myeloplipoma * Benign tumour composed of mature fat and interspersed hematopoietic elements that resemble bone marrow * Operative * Indications for adrenalectomy * Size: +4cm * 25% of tumours \>6cm will be carcinoma therefore require adrenalectomy * Suspicious for malignancy on imaging * Functional * If functional consider perioperative steroids * Approach * Open vs lap * Transperitoneal vs retroperitoneal

Answer 37

* **Aetiology & risk factors:** * Most sporadic * Southern Brazilian children * Genetic conditions * MEN1 * Li Fraumeni syndrome p53 (breast, osteosarcoma and brain tumour) * Beckwith widemann syndrome (IGF-2 gene, exophthalmos, macroglossia, nephromegly) * APC FAP * Lynch syndrome * Congenital adrenal hyperplasia * **Pathophysiology:** * Retinoblastoma gene and p53 * Most are _functional_ (+60%) * 40% present with metastasis * Common to produce sex hormones as the 21-hydroxylase is defective (thus shunting away from the corticosteroid pathway)

Answer 38

* Incidental/asymptomatic * Functional * Cushings syndrome (most common), primary hyperaldosteronism (minority), virilisation or femination * Mass effect * Abdominal or back discomfort * Necrosis of large lesions can cause fevers * Children usually have virilization and uncommon to have isolated cushings

Answer 39

* **Macroscopic features:** * Unencapsulated; large (200 g, 20 cm) * 90% are larger than 6cm * Variegated cut surface due to haemorrhage, cysts, necrosis * Often soft, friable intratumoral nodules; often invasion of major veins * Tend to invade adrenal vein, vena cava, adjacent kidney and retroperitoneum; may cause thromboemboli * Metastases to liver (60%), regional lymph nodes (40%), lungs (40%), peritoneal and pleural surfaces, bone, skin (anaplastic tumors) or retroperitoneum * **Microscopic features:** * For diagnosis need to demonstrate either metastasis or local invasiveness (bit like follicular carcinoma) * Ki-67 (\>5%) and the Modified Weiss criteria can be used for recurrence risk calculation

Answer 40

* CT adrenal * Protocol * Non con – measure the hounsfield units * Contrast * Arterial * Portal venous * Delayed * Washout (not that specific) * Absolute (compared to non contrast) washout * \>60% likely benign * \<60% likely a cancer * Relative washout * \>40% likely benign * \<40% likely a cancer * Fine slices through the adrenals * Other suspicious features for malignancy * Typically over 5cm, \>6cm risk is +25% * Heterogenous lesion * Haemorrhage * Invasion * Irregular margins on unenhanced CT * Denser that adenoma (attenuation \>10 Hounsfield)

Answer 41

* Patient and tumour factors * Tumour * Localised vs metastatic * If localised * Principles * R0 resection * En bloc resection of any involved adjacent organs * IVC involvement can be resected and thrombectomy * Open procedure – unacceptable local recurrence rate laparoscopic * If metastatic * Systemic treatment * Localised treatment including debulking, RFA, TACE * Radiotherapy * Non operative * Medical therapy with _mitotane_ (1,1-dichloro-2-( o -chlorophenyl)-2-( p - chlorophenyl)ethane) is used in advanced ACC * Mitotane, originally used as an insecticide, is a lipophilic agent concentrated in the adrenal cortex, where it induces necrosis by mitochondrial degeneration. Tumour response occurs at a therapeutic range of 14–20 mg/L in up to one-third of patients, though gastrointestinal and neurological side-effects are common and adrenaline sufficiency may occur. * Cytotoxic to the adrenal, reduces steroid hypersecretion by tumour cells – leads to adrenal insufficiency (requiring adrenal replacement) * Operative * Open is recommended approach – don’t want to violate tumour capsule * Transabdominal or thoracoabdominal * En-bloc resection of the perinephric fat, regional lymph nodes and adjacent organs including kidney, pancreas, liver or spleen maybe required to achieve complete resection * **Prognosis:** * 85% will have local or distant recurrence * 2 year survival is 50% * 5 year survival is 20% * TNM * T1 :\<5cm, no invasion * T2: \>5cm, no invasion * T3: any size, local invasion * T4: any size, invading adjacent organs * N1: node positive * M1: distant metastasis

Answer 42

**Rule of 10’s** - outdated :( * 10% of sporadic phaeochromocytoma are _bilateral_ * 10% are _extra adrenal_ * “Paraganglioma” * Bifurcation of the aorta * These secrete noradrenaline not adrenaline (cause there isn’t the PNMT enzyme) * 10% _familial_ * 10% are _malignant_ * 10% are _NON functional_ * 10% in children **Defintion** * Neoplasms composed of chromaffin cells, which synthesize and release catecholamines and in some instances peptide hormones * Phaeochromocytoma and extra-adrenal paraganglioma are tumours derived from catecholamine-producing chromaffin cells of neural crest origin arising in either the adrenal medulla (phaeochromocytoma) or extra-adrenal autonomic ganglia (paraganglioma) **Pathophysiology** * Most are sporadic * 1/3 of these carry a germline mutation * RET (sporadic MEN2) * VHL * NF1 * SDH (succinate dehydrogenase) * In pregnancy the gravid uterus compresses the tumour * Larger and extra adrenal lesions are more likely to be malignant **Clinical manifestation** * _Paroxysmal_ excessive secretion of catecholamines * Symptoms * Headache * Palpitations * Sweating * Pallor * Nausea * Weight loss * Fatigue * Anxiety * Often provoked by postural change, exercise, anxiety * Commonly associated with diabetes * Crisis may cause sudden multiorgan failure, stroke, death * 5% of adrenal incidentalomas are phaeochromocytomas

Answer 43

**Macroscopic features:** * The majority of extra adrenal paragangliomas occur in the abdomen, either from the sympathetic ganglia in the organ of Zuckerkandl (around the bifurcation of the aorta), around the renal hilum or at less frequent sites bladder, mediastinum * In contrast to sympathetic paragangliomas, parasympathetic paragangliomas arise more commonly in the head and neck **Microscopic features:** * Phaeochromocytoma of the Adrenal gland Scoring Scale (PASS) have been devised in order to predict malignancy * Ki67 proliferation index may be elevated in malignant phaeochromocytoma * A zellballen is a small nest of chromaffin cells or chief cells with pale eosinophilic staining. Zellballen are separated into groups by segmenting bands of fibrovascular stroma, and are surrounded by supporting sustentacular cells. A zellballen pattern is diagnostic for paraganglioma or pheochromocytoma. Zellballen is German for "ball of cells".

Answer 44

* Biochemical * 1. Free plasma metanephrines (if higher pretest probability – screening test) * These are the inactive metabolites of adrenaline and noradrenaline * 2. Urinary 24hr metanephrines (if lower pretest probability – confirmatory test) * Imaging * Functional localisation studies should accompany cross-sectional imaging prior to surgery for phaeochromocytoma * CT adrenal * 85-94% sensitive * Homogenous mass, if internal haemorrhage may be heterogenous * High hounsfield unit of 40-50 on non contrast * Don’t washout * MRI * Appears same intensity as liver on T1 * High signal on T2 due to high vascularity * Good for children and pregnancy and thorax * Delayed washout, at 10 minutes less than 50% * Functional * Gallium-68 (Ga-68) DOTA-0-Phe1-Tyr-3 octreotate (gallium Ga-68 DOTATATE)-positron emission tomography (Ga-68 DOTATATE PET) is proving to be more sensitive in some patients than I-123, CT/MRI, or * Iodine-131 or 123-metaiodobenzylguanidine (MIBG) scintigraphy – good for localisation * FDG-PET for detection of phaeochromocytoma, ACC and metastatic disease are all hot, but can help localise the a phaeochromocytoma * Avoid, selective venous sampling and biopsy * Genetic testing * If young \<50 * Multiple * Extra adrenal * Family history * Malignant * Screen PTH, calcium, vitamin D, urinary cytology for RCC, fundoscopy and thyroid USS

Answer 45

* The first priority is alpha blockade * (prazocin – selective alpha or phenoxybenzamine), then everything is elective * Dry/stuffy nose * Then beta block * Depends if resectable or not * Metastatic disease/non resectable * Symptom relief can be achieved by tumour debulking * Inhibition of catecholamine synthesis, and α- and β-adrenergic receptor blockade * External beam radiotherapy, chemotherapy, radiofrequency ablation and transcatheter arterial embolisation may have a role * Therapeutic doses of [131 I]MIBG can produce symptomatic and hormonal improvement as well as tumour regression or stabilisation * Resectable * Procedure * Lap over open (if \<6cm) * Consider bilateral adrenalectomy in MEN2, VHL * May need to do subtotal adrenalectomy if bilateral * Don’t remove them intraoperatively if found by co incidence * Perioperative care * Alpha adrenergic blockade (phenoxybenzamine) * Fluid resuscitation (as they are volume deplete, and can eat salt) * After alpha blockade then introduce Beta blockade (unopposed alpha blockade causes hypertensive episode and pulmonary oedema) * The period of preoperative blockade allows intravascular volume expansion to occur and cardiomyopathy secondary to chronic hypertension to resolve * Arterial and venous lines * Avoid handling the tumour * Intravenous administration medication for * Hypertensive episodes * IV magnesium * The short-acting vasodilator sodium nitroprusside * Calcium channel blocker nicardipine * α-adrenergic receptor anatagonist phentolamine * Tachycardia and arrhythmia * B blocker * Hypotension may occur post operatively thus needing HDU * Consider steroid stress dosing * Monitor _BGL_ because the lipolytic, glycolytic and glycogenolytic affects of the catecholamines has been removed * Pregnancy * Alpha adrenergic blockade, elective caesarean in third trimester * Vaginal delivery contraindicated * Early adrenalectomy post partum or in second trimester * **Prognosis:** * Follow-up fractionated urinary metanephrines are measured and repeated annually for life to exclude recurrence or further new disease

Answer 46

* **Definition:** * Constellation of signs and symptoms attributable to chronically inappropriately elevated glucocorticoids levels * **Incidence/epidemiology:** * True incidence unknown 0.1-1 per 100,000 * **Aetiology & risk factors:** * ACTH dependent * Pituitary adenoma (65% of endogenous) * Ectopic adenoma or carcinoma (small cell lung) * ACTH independent * Adrenal tumour * Adenoma 90% * Carcinoma 10% * Drugs * Bilateral adrenal hyperplasia * **Clinical manifestations:** ( see table) * **Investigations:** * Exclude medication related * Biochemical diagnosis * 1. Screening test = Hypercortisolaemia * Late night salivary cortisol * 1mg overnight dexamethasone suppression test * 2x 0.5mg tablets, take the 1mg at 11pm, then have cortisol levels taken at 8AM * If elevated cortisol despite dexamethasone then it is positive do urine * 2. Confirmatory test * 24hr urinary free cortisol * 3. ACTH level (independent vs dependent) * Imaging - adrenal * CT (triple phase adrenal) * Benign * Size \<3.5cm * \<10 Hounsfield units * If \>10 but washout \>60% in 15 minutes * Malignant * Size \>3.5 * Local invasion, heterogenous * Multiple different hormones especially virilizing * Measure DHEA * \>10 Hounsfield units and washout \>60% at 15 minutes * MRI scan * Low fat content * High enhancement and long washout with gadolinium * Investigation on ACTH dependent * High dose dexamethasone test (most pituitary sources will be suppressed) * Inferior petrosal sinus catheterization * Imaging * MRI brain * CT chest (bronchial carcinoid) * **Treatment:** * Operative * Surgery mainstay for all * Bilateral adrenalectomy for failed pituitary surgery or if no source of the ectopic ACTH is found * Localised tumour then laparoscopic approach * Beware complications (wound infection, skin injury, fractures, hypoglycaemia, adrenal insufficiency)

Answer 47

* A group of syndromes, typically autosomal recessive. * An inherited enzyme deficiency that blocks one of many enzymes involved in steroid synthesis. * The most common **21-hydroxylase** (90%). * Failure of the negative-feedback loop leads to ACTH excess and adrenal cortical overstimulation hyperplasia → build up of steroid precursors → excess of adrenal androgens. * The high levels of androgens causing virilisation (ambiguous genitalia in females). * Associated with urinary salt wasting, diarrhoea, hypovolaemia, hyponatraemia and hyperkalaemia. * Most can be managed by diagnosis and replacement of the missing steroid hormone. Not great quasimneumonic: A = aldosterone (hypertension, hypokalaemia) T = testosterone (virilisation) Before you have sex your blood pressure goes up Replace the 1 with a up arrow 21 Hydroxylase deficiency 17a Hydroxylase deficiency 11b Hydroxylase deficiency

Answer 48

Conns syndrome "Over the past 60 years, three facts have become clear: First, primary aldosteronism (PA) is more common than previously thought, and it affects between 5 and 10 percent of all patients with hypertension. Second, most patients with PA are normokalemic. Third, PA has more than one cause, and most patients with PA have bilateral idiopathic hyperaldosteronism (IHA).” **Definition:** * Autonomous adrenal cortical tissue secreting excessive aldosterone **Incidence/epidemiology:** * 5% of hypertensive patients **Pathophysiology:** * Most commonly caused by a single benign adenoma * Adenoma (60%). * Bilateral (micronodular) adrenal hyperplasia (40%) * Less commonly * Aldosterone producing adrenocorticocarcinoma * Glucocorticoid remediable hyperaldosteronism (dexamethasone suppressible \<1%, familial) * Aldosterone is the final common product of the hydroxylase enzyme pathway pregnenolone → progesterone→ corticosterone → aldosterone. * Aldosterone controls reabsorption of Na+ in the DCT via Na+/K+ and H+ pumps. Followed by H2O and so volume. **Clinical manifestations:** * Typically found on investigation of resistant HTN or hypokalaemia. * Incidentaloma * Symptoms of hypokalaemia * Cramps * Muscle weakness * Palpitations * Polyuria **Investigations:** * Screening tests * Blood pressure * Potassium level * Ratio renin:aldosterone (\>30 indicates primary) has a 90% sensitivity. * Must stop ACEI and all diuretics (frusemide, spironolactone). * Early on K⁺ will be normal in primary hyperaldosteronism * Confirmatory test * Admission for a saline/sodium loading (Demonstrate raised aldosterone despite salt and H₂O overload with 5g salt PO for 5/7 prior, then 2-3L of IV N/S in 4-6/24, then measure renin: aldosterone level * Fludrocortisone suppression test * Good if on multiple antihypertensive * 5 day admission required * 0.1-0.2mg 6 hourly Fludrocortisone plus sodium chloride and potassium – should suppress aldosterone levels * Localisation: * CT – 3mm adrenal cuts, MRI. * Adrenal venous sampling * Helps to avoid removing an adrenal due to a lesion that isn’t functional, may be difficult to lateralize if hyperplasia and not gross * Adenoma producing lesion typically very small – and a lesion seen might be not responsible for the Conn’s * Invasive, sample the venous blood from the adrenal glands * If \>35-40 then AVS needed * This is important to know for the exam **Treatment:** * Post diagnosis correct BP and K+. * Plan lap adrenalectomy if: * Patient \<40 years. * Mass \>1cm. * Normal contralateral gland. * IF not: selective venous sampling (aldosterone, cortisol, renin) via an IVC catheter may identify a dominant gland or bilateral disease. * Fludrocortisone suppression test may be helpful. * Patients with glucocorticoid-remediable hyperaldosteronism should be treated with steroids. * Spironolactone **Prognosis** * At best ⅔ of patients are cured by surgery, the majority will experience a benefit from reduced medication requirements

Answer 49

* **Definition:** * Inadequate production &/or release of corticosteroids * **Aetiology & risk factors:** * Primary adrenal insufficiency * Autoimmune (Addison’s Disease) * Tuberculosis * Bilateral adrenal haemorrhage, infection or neoplasm * Waterhouse-Fredrickson syndrome (meningococcal) * Heparin induce thrombocytopaenia * Secondary adrenal insufficiency * Tertiary adrenal insufficiency * Exogenous steroid use * Anything effecting hypothalamus * **Pathophysiology:** * Stress - both mineralocorticoid and glucocorticoid deficiency can participate in the development of adrenal crisis. * The physiologic basis for this is the ability of aldosterone or synthetic mineralocorticoid to promote sodium retention as well as to enhance vasoconstrictor responses of the vasculature * Glucocorticoid deficiency can contribute to hypotension by causing decreased vascular responsiveness to angiotensin II and norepinephrine, decreased synthesis of renin substrate, and increased prostacyclin production * **Clinical manifestations:** * Chronic * Fatigue * Weakness * Weight loss * Electrolyte imbalance (low sodium, high potassium, anaemia, hypoglycaemia) * Skin pigmentation * Acute * Acute illness/stress response precipitant * Same as above + * Abdominal pain * Fevers (do assume fever is secondary to infection) * Confusion-coma * Hypotension tachycardia * Addisonian crisis * Refractory shock/hypotension * Unresponsive to inotropes * **Investigations:** * Biochemistry * 8AM serum cortisol and ACTH * ACTH stimulation test * Renin aldosterone levels * Abdominal CT * **Treatment:** * Treat before making diagnosis * Hydrocortisone * Perioperative (stress dosing) * None if 5mg/day for upto 3 weeks * Intermediate (between these two groups) do 8am fasting cortisol level (24hrs since steroid dose) * If \>20mg/day for 3 weeks * Minor surgery - just take regular dose * Moderate surgery - 50mg IV before induction then 25mg TDS for 24 hrs * Major surgery - 100mg IV before induction then 50mg TDS for 24 hrs. Then taper by half per day to maintenance level

Answer 50

Unresectable metastatic disease * Long acting somatostatin analogues * Ablation * Embolisation * Chemotherapy * TKI (sumatinib) * MTOR inhibitors (everolimus) * Interferon alpha * Somatostatin analogues (octreotide) * Peptide receptor radionuclide therapy – radioactive somatostatin analogues (Lutetium 177 dotatate)

Answer 51

Unresectable metastatic disease * Long acting somatostatin analogues * Ablation * Embolisation * Chemotherapy * TKI (sumatinib) * MTOR inhibitors (everolimus) * Interferon alpha * Somatostatin analogues (octreotide) * Peptide receptor radionuclide therapy – radioactive somatostatin analogues (Lutetium 177 dotatate)

Answer 52

\>4cm Suspicious features Functional

Answer 53

Cushingoid Cataracts Ulcers Striae and skin thinning Hypertension and hirsutism Immunosuppression and infections Necrosis of femoral heads Glucose elevation Osteoporosis and obesity Impaired wound healing Depression and mood changes

Answer 54

**Cell origin** Beta **Facts** Most common 0.1 per 100,000 90% Benign F\>M \>99% pancreatic 10% multiple 10% familial **Manifestations** Cherry red or brown lesion Hypoglycaemia Weight gain Whipples triad: Fasting Low sugar \<5 Symptomatic (Neuroglycopaenic + ANS activation) Better with IV glucose **Diagnosis:** Fasting BGL \<3 High insulin \>3 High C peptide High proinsulin 50% too small for standard imaging EUS then Ca arteriography IOUS Octreotide scan doesn’t work **Medication management** High carb diet 2nd line diazoxide (inhibits insulin release) Octreotide (30% respond) mTOR inhibitors **Surgical management** Intraoperatively check for multiple pancreatic lesions, kocherisation + opening the lesser sac Enucleation or oncological resection if malignant

Answer 55

**Cell origin:** G cells **Facts:** 60-90% malignant and 40% with liver metastases ⅔ in duodenal wall 80% in gastrinoma triangle [Juncs of Neck-body/CD-CBD /D2-D3] 1:4 MEN1 Sporadic = larger/solitary **Manifestations:** ZES Epigastric pain Diarrhoea Oesophagitis Duodenal or jejunal ulceration **Diagnosis:** Fasting gastrin level \>100 (PPI false positive) If \<1000 then do a secretin test Gastric pH \<2 Endoscopy CT/MRI/somatostatin receptor scintigraphy EUS 2^nd line ASVS 3^rd line IOUS **Medical management:** High dose PPI (beware low B12 and Mg) MEN1 might have only medical management (small & multifocal ++), sort out the parathyroid Mets: octreotide, resection, embolisation, transplant **Surgical management:** Duodenotomy to check for occult gastrinoma are nearly always in the duo Formal resection + peritumoral lymph nodes

Answer 56

**Cell origin:** Alpha cells **Facts:** 90% malignant F\>M Body and tail of pancreas **Manifestations:** 4 D's Diarrhoea DVT Dermatitis Diabetes Weight loss Necrolytic migratory erythema (NME) - blistering rash in groins, leg and anogenital **Diagnosis:** High glucagon levels Mild-moderate DM **Medical management:** Octreotide Thromboprophylaxis IV amino acid infusion (deficiency causes NME) **Surgical management:** Distal pancreatectomy + LN dissection +/- splenectomy +/- cholecystectomy - not enucleation

Answer 57

**Cell of origin:** D2 cells of the pancreas **Facts:** 50% malignant Rare Usually solitary Distal pancreas Can be extrapancreatic (adrenal, retroperitoneal or mediastinum) **Manifestations**: "WDHA syndrome" - pancreatic cholera Watery diarrhoea 5L per day! Hypokalaemic achlorydia **Diagnosis:** High VIP levels Low potassium Metabolic acidosis **Medical management:** Octreotide Correct electrolytes **Surgical management:** Oncological resection Cholecystectomy

Answer 58

**Cell origin:** D cells **Facts:** Extremely rare Found in either HOP or D2 Decreases hormone secretion 70% malignant **Manifestations:** Diarrhoea Steatorrhea Malabsorption DM Cholecystitis **Diagnosis:** High somatostatin levels **Medical:** Octreotide (somatostatin receptor analogues) **Surgical:** Oncological resection + cholecystectomy

Answer 59

**Cell of origin:** Enterochromaffin cells - EC cells are proposed to be specialized mechanosensory cells that release serotonin in response to epithelial forces, and thereby regulate intestinal fluid secretion. **Facts:** NET of mid gut Small 80% are APUDomas **A**mine **P**recursor **U**ptake – for high uptake of amine precursors including 5-hydroxytryptophan ([5-HTP](https://en.wikipedia.org/wiki/5-Hydroxytryptophan)) and dihydroxyphenylalanine ([DOPA](https://en.wikipedia.org/wiki/L-DOPA)). **D**ecarboxylase – for high content of the [enzyme](https://en.wikipedia.org/wiki/Enzyme) [amino acid decarboxylase](https://en.wikipedia.org/wiki/Amino_acid_decarboxylase) (for conversion of precursors to amines).) **Manifestations:** Asymptomatic Carcinoid syndrome * face neck flushing * Diarrhoea * Bronchospasm * Right heart valve disease **Diagnosis:** Blood chromogranin A Urine 24 hours 5 HIAA Echo **Medical management:** Octreotide Liver mets: resect/embolise/ablation _Pre-Op Carcinoid Syndrome_: ECHO / Octeotride Infusion / Betablockers / Antihistaminics and Hydrocortisone infusion to avoid Carcinoid Crisis (bronchoconstriction – fever – arrhythmia – shock – flushing) **Surgical** Resect Adjuvant

Answer 60

* Space of Reeve: avascular plane between upper pole of thyroid and cricothyroid muscle * Joll's triangle superior insertion of strap muscles, upper pole of thyroid (lateral) and midline trachea (medial)

Answer 61

* Tubercle of zuckerkandle; nerve lies posteriomedial to this projection * Ligament of Berry; the nerve lies lateral to this * Simons triangle; common carotid lateral, oesophagus medial, interior thyroid artery superior

Answer 62

* Non recurrent laryngeal nerve, associated with arteria lusoria (abberant R subclavian off the aortic arch **distal** to L subclavian) where the R subclavian artery doesn’t come of the right brachiocephalic trunk, but directly off the arch of the aorta distal to the left subclavian artery, where it passes posterior to the oesophagus * The nerve in this situation, the nerve doesn’t travel in the inferior to superior orientation but from the lateral to medial directly off the vagus – in this situation it is at risk in thyroidectomy

Answer 63

* To enter into the larynx at the inferior border of the inferior constrictor (cricopharngeus)

Endocrine Flashcards

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