Endocrine Surgery Flashcards

Question

Hx & Clinical Features suggestive of malignancy of thyroid nodule

Answer 1

_History:_ * *1) Rapid size increase 2) Pressure symptoms** e.g. RLN palsy * *3) Previous history of neck RT 4) Family history of thyroid cancer** _Physical Exam:_ * *1) Hard consistency, irregular surface 2) Fixed / tethering to surrounding structures** * *3) Solitary nodule 4) Cervical lymphadenopathy** *("Hot" nodules i.e. hyperthyroidism is usually benign)*

Answer 2

* *1) Blood test** - Thyroid function: TSH, fT4 - CaPO4 - CEA and Calcitonin if suspicious of medullary carcinoma * *2) USG Thyroid & Neck +/- FNA** - distinguish cystic and solid nodule - note malignancy features - guide FNA - FNAC based on Bethesda classification, molecular assay _Additional Investigations:_ * *4) Other Imagings (usually not needed)** - 123-iodine Radioisotope scintigraphy (esp when FNA is indeterminate) for function - CT neck and thorax to delineate anatomy to guide operation; as well as if suspicious of ETE or LN mets in cancer * *5) Laryngoscopy/OGD** - for cord check pre-operatively

Answer 3

* *1) Thyroid USG +/- FNAC** - first line -\> quick, non-invasive, non-irradiating - features suggestive of malignancy, assess cervical LN status - FNAC * *2) Radioisotope Thyroid Scan** (thyroid scintigraphy) is uncommonly used for: - when cause of hyperthyroidism is unclear - assess ectopic thyroid tissue - assess remnant post-op thyroid tissue - surveillance of thyroid cancer * *3) Neck and thorax CT** - for anatomical overview of large goitres, especially to assess retrosternal extension and pressure effect on surrounding structures - If cancer with suspicious extra-thyroid extension, or clinically multiple/bulky LNs

Answer 4

* *High suspicion of Malignancy if any 1 of:** 1) Irregular margins 2) Taller than wide shape 3) Microcalcifications 4) Disrupted rim calcifications 5) Extrathyroidal extension * *Intermediate suspicion of malignancy:** 1) Solid _hypoechoic_ nodule 2) Solid _hypoechoic_ nodule in partially cystic nodule * *Low suspicion:** 1) Solid isoechoic or hyperechoic * *Very low suspicion:** 1) Partially cystic, spongioform * *No suspicion, must be benign:** 1) Purely cystic

Answer 5

Based on the ATA guideline, we must consider based on the **size, US features, and clinical presentation**; perform FNAC if: **1) US features suggestive of malignancy** * *2) Sufficient size** - 1cm if high / intermediate suspicion - 1.5cm if low suspicion - 2cm if very low suspicion * *3) Clinical features worrisome:** - Associated cervical lymphadenopathy - Dominant or atypical nodules in multinodular goitre - Complex or recurrent cystic nodules

Answer 6

I. Non-diagnostic II. Benign III. AUS (atypia) or FLUS (follicular lesion) IV. Follicular neoplasm V. Suspicious of malignancy VI. Malignant

Answer 7

_Papillary thyroid cancer:_ * *- BRAF** (papillary thyroid carcinoma) * *- RET-PTC** (papillary thyroid carcinoma) _Medullary thyroid cancer_ **- RET** (associated with MEN2a, 2b)

Answer 8

i.e. Thyroid nodule -\> non-diagnostic **1) Repeat USG + FNAC** 2a) If other bethesda classes, then manage accordingly 2b) If Bethesda I again, then consider diagnostic hemithyroidectomy if worrisome features: * High USG suspicion * Growing nodule (\>20% increase in 2 dimensions) * Clinical risk factors - previous neck irradiation - familial thyroid cancer - fixation to surrounding tissues - vocal cord palsy - suspicious neck LN

Answer 9

``` _Class III (AUS or FLUS)_ **1) Repeat USG + FNAC** if no worrisome features ``` * *2) Proceed with surgery** if worrisome features, i.e. - suspicious USG - growing nodule (\>20% in 2 dimensions) - clinical suspicion (prior neck RT, family Hx, fixation, VC palsy, neck LN) * Hemithyroidectomy * Total thyroidectomy if high risk: - suspicious of ETE - prior neck RT - family Hx of thyroid cancer - size \>4cm - BRAF mutation +ve - bilateral nodular disease ``` _Class IV (Follicular Neoplasm)_ **1) Hemithyroidectomy** ``` **2) Total thyroidectomy** if high risk, i.e.: * suspicious of ETE * prior neck RT * family Hx of thyroid cancer * size \>4cm * BRAF mutation +ve * bilateral nodular disease

Answer 10

Histological diagnosis: * *1) Papillary (70%)** - Best prognosis - Slow growing, late mets - Common cervical node metastasis (via lymphatics in neck) - Pathology: "orphan Annie eye" - a/w irradiation * *2) Follicular (15%)** - Slow growing, but more malignant than papillary - Locally invasive, also hemat spread with 20% distant met - a/w iodine deficiency "endemic goitre" * *3) Medullary (3%)** - From parafollicular C cells, thus calcitonin and CEA - 1/3 = sporadic; 1/3 = familial (FMTC); 1/3 = MEN 2A or 2B - Patho: amyloid found between tumour cells * *4) Anaplastic (5%) i.e. undifferentiated** - very high mortality, rapid growing - early local invasion, to trachea/esophagus - early nodal mets - early haematogenous spread to lungs, bone and brain - More common in elderly; possible progression from longstanding follicular or papillary thyroid CA

Answer 11

_Multiple Endocrine Neoplasm_ These are a group of inherited disorders (**autosomal dominant**) where affected individuals develop tumours in two or more endocrine glands at the same time, making the affected glands overactive. MEN I MEN IIA, IIB

Answer 12

* *_MEN-1 (MENIN gene; AD)_** 1) 4-gland hyperparathyroidism (usu presented first) 2) Pituitary adenoma (usu prolactinoma) 3) Pancreatic islet cell tumour - usu gastrinoma with ZES - insulinomas, glucagonomas, VIPomas, PPomas **_MEN-2 (RET proto-oncogene; AD)_** **MEN-2A** 1) Medullary thyroid carcinoma (variable course; presented first) 2) Hyperparathyroidism 3) Pheochromocytoma (in 50%) +) GI manifestation e.g. abdominal pain & distension, Hirschsprung disease ("MEN-2A-HD") **MEN-2B** 1) Medullary thyroid carcinoma (very early & aggressive!) 2) Ganglioneuromatosis, mucosal neuroma 3) Pheochromocytoma +) GI e.g. megacolon +) Dysmorphism: hypergnathism, marfanoid body habitus **FMTC** (familial medullary thyroid carcinoma)

Answer 13

Similar to thyroid nodules, but additional investigations: * *1) Thyroid USG + FNAC** - esp look for any ETE - genetic testing for tissue (BRAF, RET) * *2) Neck USG** - for cervical nodal status **3) Laryngoscopy/OGD** for cord check * *4) Contrast CT:** - CT neck if suspected ETE or LN mets _Additional workup for Medullary Thyroid Carcinoma:_ **5) Tumor markers**: Calcitonin and CEA * *6) MEN 2A/B screening:** - 24hr urine metanephrines x3 (rule out pheo) - CaPO4, PTH (rule out primary hyper-parathyroidism) * *7) Metstatic workup** if high calcitonin \>500 - CT Neck + T + A - Bone scan

Answer 14

_A. Surgery_ * *1) Hemithyroidectomy or Total thyroidectomy** - total thyroidectomy if * \>4cm * N+, M+, T4 * Risk factors e.g. fam history, prior neck RT, bilateral * *2) Central neck compartment dissection** - prophylactic if T3/4, or T1b - therapeutic if level VI positive (T1a) * *3) Ipsilateral modified radical Neck dissection** - therapeutic if T1b (level I-V) _B. Post-op management_ **4) RAI therapy** as adjunct (if total thyroidectomy, high risk) **5) Lifelong TSH suppression** with thyroxine **6) Calcium management** if needed **7) Surveillance USG and Thyroglobulin**

Answer 15

Complete total thyroidectomy for PTC if: 1) T4 disease (gross ETE to structures apart from straps) 2) Nodal +ve 3) Bilateral or multifocal (e.g. MNG)

Answer 16

_A. Surgery_ **1) Total thyroidectomy in all** * *2) CCD in all** (except palliative surgery in M1) - prophylactic CCD if workup LN -ve - therapeutic CCD if workup LN +ve * *3) MRND** - ipsilateral if central node +ve - bilateral if ipsilateral node +ve _B. Adjuvant therapy_ **4) Adjuvant RT** _C. Palliative therapy_ **5) Tyrosine Kinase Inhibitors** (Anti-RET) after total thyroidectomy _D. Follow-up_ **6) Monitor Calcitonin, CEA, surveillance USG** **7) Thyroxine replacement, no need TSH suppression** * *8) Hypocalcemia management** (2) CEA

Answer 17

**1) Previous neck RT** * *2) Family history of thyroid cancer** - BRAF mutation for PTC - RET gene for MEN2A/B (MTC) **3) Female** **4) Asian race**

Answer 18

**1) Malignancy** (PTC/FTC/MTC) * *2) Thyroid nodule** - diagnostic hemithyroidectomy (in view of risk of malignancy but FNAC unable to differentiate benign from malignant) **3) Thyrotoxicosis** (selected cases) * *4) Large goitre** - with pressure Sx - cosmetic purpose due to patient preference

Answer 19

1) TFT, CaPO4 2) If thyrotoxicosis, need cardiac workup: - ECG - Echocardiogram 3) Triple assessment of thyroid nodule - USG +/- FNAC 4) OGD / laryngoscopy for VC status check

Answer 20

**_Hemithyroidectomy_** = Unilateral lobectomy + isthmusectomy + safer + low chance of hypothyroidism, no need lifelong thyroxine replacement - may require re-operation on contralateral lobe **_Total thyroidectomy_** + lower recurrence + Allows radioiodine ablation therapy + Allows thyroglobulin monitoring - additional risk (e.g. hypoparathyroidism, hoarseness of voice) - Hypothyroidism, thus need levothyroxine replacement

Answer 21

**Transverse collar incision** _Landmark:_ - 2 cm above the sternal notch in Langer’s lines - Extend incision as far laterally as the medial border of sternocleidomastoid

Answer 22

_Vessels that need to be ligated:_ - superior and inferior thyroid artery - superior, middle, and inferior thyroid vein _Which vessel first:_ - **middle thyroid vein** should be ligated and divided first - enable you to dislocate the lobe medially and continue dissection

Answer 23

* Skin * Subcutaneous fat * Platysma * Investing layer of deep cervical fascia * Strap muscles (sternohyoid and sternothyroid) * Pretracheal fascia * False sheath of connective tissue overlying the thyroid * Isthmus of the thyroid gland

Answer 24

_A. General_ 1) General GA complications 2) General surgical complications - pain, surgical site infection, scar ============================ _B. Specific complications_ _Early_ * *1) Bleeding, haematoma** - potential airway compromise and asphyxia from laryngeal oedema * *2) RLN injury** - vocal cord palsy if unilateral (about 30% transient; 10% permanent) - airway compromise if bilateral * *3) EBSLN injury** - lower voice, cannot reach higher frequency (due to cricothyroid palsy) **4) Pneumothorax, pneumomediastinum** **5) Thyroid storm, tracheomalacia** (uncommon) _Chronic:_ **1) Hypothyroidism** * *2) Permanent hypoPTH (hypoCa)** - transient (e.g. parathyroid inflammation) - permanent (e.g. resected) if after 6 months

Answer 25

Always have a pair of **suture cutting scissors** or **clip removers** In case of wound haematoma and upper airway obstruction: - O2 therapy - remove dressing - suture and clips removed immediately, remove haematoma at bedside - book EOT for formal exploration and closure of the wound afterwards

Answer 26

It is because: * *1) Laryngeal oedema** - Thyroid surgery involves closing the fascial planes around the neck - thus haematoma develops within a confined space - thus results in impaired laryngeal venous return - thus laryngeal oedema * *2) Tracheomalacia** is sometimes seen with very large thyroid - thus to haematoma may compress on the airway (!! without tracheomalacia, the haematoma does not lead to direct airway compression)

Answer 27

_Resp, Cardi, neuro (sensory + motor), eye, bone_ **1) Hyperventilation; laryngeal spasm, stridor, apnoea** **2) Cardiac arrhythmias - Long QT** * *3) Increased neurmuscular irritability** - Paraesthesia - circumoral numbness - Tetany (Trousseau’s sign, Chvostek’s sign, hyperactive deep tendon reflex) - Convulsion (Grand mal seizures) **4) Cataracts** **5) Rickets & osteomalacia**

Answer 28

* *1) Hyperreflexia** - hyperactive deep tendon reflex * *2) Trousseau’s sign** - Carpal spasm if BP cuff inflated higher than systolic BP for 3 min * *3) Chvostek’s sign** - facial muscle contraction upon tapping of facial nerves

Answer 29

* *1) Pseudohypocalcaemia** (low albumin) - NO hypocalcemic symptoms * *2) Hypoparathyroidism** - post-surgical - idiopathic, familial * *3) Pseudohypoparathyroidism** - end organ resistance to PTH * *4) Vitamin D / calcium deficiency** - diet; malabsorption, bisphosphonates - chronic renal disease * *5) Abnormal vitamin D synthetic pathway** - 1α hydroxylase deficiency - 1,25 (OH)2 VitD resistance * *6) Altered bound calcium** - pH changes; citrate use; hyperphosphatemia - acute pancreatitis

Answer 30

* *1) IV Ca gluconate** bolus - with cardiac monitor - slow injection of 10ml 10% * *2) PO Ca replacement:** - CaCO3 tablets ~3000mg BD - Rocaltrol (i.e. Vitamin D3) ~ 2.5mcg BD * *3) Monitor serum adjCa level** - up to Q6H

Answer 31

* *1) Hormonal regulation** - PTH - 1, 25 DOH Vit D - calcitonin - others like cortisol (bone resorption) TH (bone growth) GH (bone growth) Estrogen (prevent osteoporosis) * *2) Nonhormonal regulation** - Albumin-bound calcium (40% of plasma Ca) - Phosphate & pH (both affects ionic Ca level) - Exchangeable pool in bone (amorphous calcium phosphate)

Answer 32

No, as around 40% of serum Ca are bound to albumin, thus with hypoalbuminaemia, total calcium may be low yet ionized calcium might be normal. Measurement of ionised Ca will be more accurate. We can also estimate the Ca by calculating the "adjusted or corrected Ca": **Adjusted Ca = Total Ca + [0.02 \* (40 - albumin in g/L)]**

Answer 33

**1) PTH** (increase Ca and decrease PO₄) * Increased Ca release from enhanced bone resorption via osteoblasts & osteoclasts * Increased distal convoluted tubules Ca reabsorption (and increased proximal convoluted tubules phosphate excretion) * Increased uptake of calcium from intestine by promoting kidney formation of 1,25(OH)₂ Vit D3 **2) Vitamin D** (increase Ca) * Increased calcium uptake in intestine by increased calcium binding protein * Increased bone resorption and Ca release (in high doses) * Permission role on PTH action on bone **3) Calcitonin** (decrease Ca and decrease PO₄) * Decreased bone resorption via inhibition of osteoclasts * Decreased reabsorption of calcium from kidney (and promotes phosphate excretion)

Answer 34

**Inferior thyroid artery** (from thyrocervical trunk from 1st portion of subclavian artery)

Answer 35

"Stones Bones Groans Psy overtones" **1) Polyuria, polydipsia** * *2) Stones** - renal stone - nephrocalcinosis - renal failure, hypertension - gout * *3) Bones** - Bone pain - Joint pain (cartilage calcification) - osteopenia with reduced bone mineral density (esp cortical bone e.g. distal 1/3 of forearm) - fracture - Osteitis fibrosa cystica * *4) Groans** - Muscle pain & weakness - dyspepsia - constipation - peptic ulcer disease - pancreatitis * *5) Psychiatric overtones** - depression, anxiety - sleep disturbances - fatigue, lethargy - anorexia

Answer 36

* *1) Primary hyperparathyroidism** - parathyroid adenoma (usu 1 gland) - parathyroid hyperplasia (usu 4 glands) - parathyroid carcinoma (very rare) * *2) Tertiary hyperparathyroidism** - in uncorrected secondary hyperparathyroidism, usu from hypocalcemia due to chornic renal failure, vitamin D deficiency **3) Hypercalcemia of malignancy** * *4) Hypocalciuric hypercalcemia** - Familial hypocalciuric hypercalcemia (mutation of calcium sensing receptor CaSR) - thiazide * *5) Vitamin D excess** - granulomas i.e. TB, sarcoidosis (increased production & absorption) * *6) Increased bone turnover** - Hyperthyroidism - Paget's disease

Answer 37

As a result of chronic hypocalcemia, there is a physiological hypersecretion of PTH. Note the serum calcium is usually low or normal-low. Usually due to: * *1) Chronic renal failure** - phosphate will be high * *2) Vitamin D deficiency** - phosphate will be low **3) Renal hypercalciuria**

Answer 38

Prolonged secondary hyperparathyroidism may result in parathyroid hyperplasia and autonomous secretion of PTH, leading to tertiary hyperparathyroidism and hypercalcemia. Note: **high PTH, high Ca, high phosphate**

Answer 39

_LAB TEST_ 1) Serum Ca, PO₄^2- ; note calculate the Adjusted Ca level 2) Urine Ca, PO₄^2-(note hypercalciuria in hyperPTH; if low, then hypocalciuric hypercalcemia) 3) PTH, Vit D, Calcitonin 4) Urine cAMP 5) Chloride/phosphorus ratio (if \>33 then primary hyperparathyroidism) 6) Serum ALP, Urine hydroxyproline (to screen for bone diseases) 7) RFT for Urea, creatinine, eGFR (for renal failure) 8) 24 hour urine 9) Tumour markers if suspecting malignancy, esp Calcitonin for MTC in MEN2a 10) Test for MEN and RET gene _IMAGING STUDIES_ 1) KUB, Abdomen USG, CT for renal stone, nephrocalcinosis 2) Parathyroid USG 3) Nuclear Scintigraphy for parathyroid activity - parathyroid sestamibi scan - SPECT (single-photon emission CT) 4) X ray of bones and joints - see if it's pathological fracture 5) DEXA scan - for bone mineral density (BMD) - Vertebral spine assessment

Answer 40

- Water, remove water, bisphosphonates, calcitonin, mithramycin, dialysis - Corticosteroid, prostaglandin inhibitor, denosumab * *0. Dialysis** - Last resort... useful when other methods fail * *1. Replacement of fluids** - Use isotonic saline to promote natriuresis & renal Ca clearance - Monitor fluid and electrolyte balance * *2. Frusemide** - To increase urinary calcium excretion - Only give frusemide after adequate fluid hydration (check adequate urine output) - avoid thiazide as it decrease urinary Ca excretion * *3. Bisphosphonates (pamidronate, etidronate)** - Decrease bone resorption - IV preparations potent and rapid onset - Currently the most commonly used treatment * *4. Calcitonin** - Rapid onset, minimal side effects - Decrease bone resorption - Fall in calcium small * *5. Mithramycin** - Direct effect on osteoclast, decreases bone resorption - Maximal fall occurs in 2 to 5 days - Side effects: marrow suppression * _6-8 for malignancy:_* * *6. Corticosteroids** - Decrease bone turnover - Useful in patients with myeloma, leukaemia, lymphoma, sarcoidosis, vitamin D intoxication * *7. Prostaglandin inhibitors** - Useful only in hypercalcaemia due to production of prostaglandins by tumours * *8. Denosumab** - for hyperCa of malignancy

Answer 41

1) Single parathyroid adenoma 80% 2) Multiple adenoma or hyperplasia 17% 3) Parathyroid carcinoma \<1%

Answer 42

**1) Can be asymptomatic** * *2) Symptomatic with signs of hypercalcemia** Polyuria + "Stones bones, groans, psychiatric overtones" - see below * *3) Symptoms of MEN 1 or MEN 2a** - pituitary tumour, pancreatic endocrine tumour - medullary thyroid carcinoma, pheochromocytoma \_\_\_\_\_ ^{1) Polyuria} ^{2) Stones
- renal stone
- nephrocalcinosis
- renal failure
- gout} ^{3) Bones
- Bone pain
- Joint pain (cartilage calcification)
- osteopenia with reduced bone mineral density (esp cortical bone e.g. distal 1/3 of forearm)
- fracture
- Osteitis fibrosa cystica} ^{4) Groans
- Muscle pain & weakness
- dyspepsia
- constipation
- peptic ulcer disease
- pancreatitis} ^{5) Psychiatric overtones
- depression, anxiety
- sleep disturbances
- fatigue, lethargy
- anorexia}

Answer 43

* *1) Bone resorption - ** cortical bone greater than trabecular bone (DEXA scan will show low bone mineral density in e.g. distal 1/3 forearm) - subperiosteal bone resorption is also common (e.g. classically on radal side of 2nd & 3rd phalanges) * *2) Demineralisation** will cause: - **bone pain & fractures - osteopenia & osteoporosis - osteolytic lesions (pepperpot skull) - bone deformities** **3) Osteitis fibrosa cystica** aka "Brown tumours"

Answer 44

* *1) Chloride/phosphorous ratio of \>33** is diagnositc - chloride is high due to PTH causing renal bicarbonate wasting **2) High Ca, low PO4** * *3) PTH** - can be **normal** (**abnormally normal**, as with hyperCa PTH should be low) - can be **high** * *4) Urine** - hypercalciuria - High urine cAMP * *5) Increased serum ALP, urine hydroxyproline** - reflects bone disease 6) DEXA scan shows reduced Bone mineral density 7) Subperiosteal bone resorption (usu on radial aspect of 2nd and 3rd phalanges)

Answer 45

* *1) Sympatomatic hyperCa** - Bone, stone, moan (constipation), psy (depression) - polydipsia **2) If asymptomatic**, then need to be: * Age \<50 * High Ca \>2.80 * Skeletal involvement - DEXA scan: T-score below -2.5 - Vertebral fracture * Renal involvement - Cr clearance \<60 ml/min - 24hr Ca \>10mmol/day - Urolithiasis

Answer 46

* *1) Pre-operative or intraoperative localisation** of the lesion - parathyoid US - Sestamibi scan/SPECT - 4DCT, MRI * *2) Intra operative PTH assay** - To monitor success of parathyroid surgery - t_1/2 of PTH is only 3.5 - 4 mins in patients with normal renal function, thus a 15 minute assay result will reflect the correction - _Miami Criterion_: Fall of 50% compared to the highest of either the premanipulation or pre-excision sample

Answer 47

* *1) Parathyroid Ultrasound with Doppler** - Pre-operative or intra-operative - Limited in its ability to evaluate retroesphageal lesions or mediastinal parathyroid glands * *2) Nuclear Scintigraphy** - Tc-99m Sestamibi Scan; with or without SPECT **3) CT, SPECT/CT; MRI etc.** * *4) 4D Computed tomography** - i.e. Multiple scans obtained afte adminstration of IV contrast scans

Answer 48

**1) Rapid correction of hypercalcemia** * *2) Minimally Invasive Surgery (the only definitive treatment)** i) if one parathyroid adenoma, then *directed unilateral neck exploration*: - _Minimal invasive parathyroidectomy_ of the involved gland only (through directed unilateral neck exploration) ii) if parathyroid hyperplasia, then *bilateral neck exploration*: - _3.5 gland parathyroidectomy_ - _Total parathyroidectomy_ with immediate _auto transplantation to forearm muscle_ iii) if suprenumerary parathyroid gland: - _Cervical thymectomy_ * *3) Medical therapy** * if surgery cannot be performed:* - Fluid replacement - Loop diuretics (frusemide) to enhance calcium excretion - Calcimimetics, i.e. _Cinacalcet_

Answer 49

**Miami Criterion** based on 15 min assay of intra-op PTH assay: - Fall of 50% compared to highest of baseline (pre-manipulation or pre-excision sample) - t1/2 of PTH is only 3.5 - 4 mins in patients with normal renal function, thus a 15 minute assay result will reflect the correction

Answer 50

* *Indication:** 1) Four-gland parathyroid hyperplasia (or other situation where all four glands are removed), esp in cases of MEN1 or 2A 2) Renal failure and secondary hyperparathyroidism * *Advantage over 3.5 gland parathyroidectomy:** 1) Allow the transplanted parathyroid tissue to be localised and re-excised under LA in case of high recurrence risk (e.g., MEN type 1 or 2A) * *Site:** 1) Sternocleidomastoid 2) Brachioradialis muscles of non-dominant forearm

Answer 51

0) GA complications, general wound complications _Specific complications:_ * *1) Neck haematoma** causing airway compromise * *2) RLN palsy 3) EBSLN palsy** * *4) Hypocalcaemia 5) Hungry bone syndrome**

Answer 52

Severe hypocalcemia seen after parathyroidectomy for primary hyperPTH Due to chronically calcium-deprived bone aggressively absorbing calcium

Answer 53

_A. CORTEX:_ From outer to inner forms "GFR", which correlates to "Salt, Sugar, Sex": * *1) Zona glomerulosa** - _mineralcorticoids_ (aldosterone, deoxycorticosterone DOC, 18 hydroxyl DOC) * *2) Zona fasciculata** - _glucocorticoids_ (cortisol, corticosterone) * *3) Zona reticularis** - _androgen_ (dehydroepiandrosterone, androstenedione and testosterone) _B. MEDULLA_ * *4) Chromaffin cells** - release _catecholamine_ (epinephrine & norepinephrine) under sympathetic stimulation

Answer 54

_Arteries:_ **1) Superior adrenal artery** (from inferior phrenic artery) **2) Middle adrenal artery** (branch of the aorta) **3) Inferior adrenal artery** (branch of the renal artery) _Venous drainage:_ **1) Right adrenal vein** drains into the IVC **2) Left adrenal vein** drains into the left renal vein

Answer 55

* *Left adrenal gland:** - drained by left renal vein * *Right adrenal gland:** - drained by IVC

Answer 56

Cortical vs Medullary; functional vs non-functional: _Cortical functional_ * *- Cushing's** (Cortisol secreting adrenal adenoma) * *- Conn's** (Aldosterone secreting adrenal adenoma; Idiopathic bilateral adrenal hyperplasia) - Adrenocortical carcinoma (can be Cushing's, Conn's, or virilisation) _Cortical non-functional_ * *- Adrenocortical adenoma - Adrenal myelolipoma - Adrenocortical carcinoma - Adrenal metastases** - "Collision tumour" _Medullary_ * *- Pheochromocytoma** - Neuroblastoma (in \<4yo) - Sympathoblastoma - Ganglioneuroma

Answer 57

Incidentally discovered adrenal masses usu in CT Majority are non-functional **adrenocortical adenoma**.

Answer 58

_A. Is it functional?_ **1) Symptoms and clinical examination** * *2) Cushing's** - 1mg ONDST to look for unsuppressed cortisol * *3) Conn's** (primary hyperaldosteronism) - first stop interfering meds for 4 weeks (alpha blocker, beta-blcoker, ACEI, ARB, diuretics) - then check RFT, renin, aldosterone (look for high ARR) * *4) Sex hormones** - testosterone, DHEA, 17-beta estradiol * *5) Pheochromocytoma** - 24-hour catecholamines _B. Is it malignant?_ **1) Any known history of malignancy** **2) CT adrenal with contrast** **3) CT-guided FNA** if needed

Answer 59

1) Size ≥4cm 2) Irregular border 3) Heterogeneous pattern 4) Central calcifications 5) HU \>20 on non-contrast CT 6) Relative washout \<40%, or absolute washout \<60% --\> Suspicious of malignancy, may need FNA and adrenalectomy

Answer 60

Depends on function or CT findings: 1) If suspicious CT features or functional lesion: - \> **lap adrenalectomy** 2) If not suspicious, not functional: - monitor clinical symptoms and sign - monitor biochemical test yearly - monitor radiological features yearly: if Interval growth \>1cm in 1-2 years, then indicated for adrenalectomy - if \<4cm: monitor clinically, biochemically, radiologically with CT annually - if enlarges ≥1cm in first 2 years: adrenalectomy - if ≥4cm: adrenalectomy

Answer 61

* *_Dual blood supply_** 1) Portal blood in corticomedullary sinuses having previously drained the adrenal cortex 2) Medullary arteries

Answer 62

- Both can produce noradrenaline (Major pathway and enzymes required for catecholamine biosynthesis are the same) - Only adrenal medulla can produce adrenaline by methylation of noradrenaline

Answer 63

* *1) Noraderenaline** - α1 and β1 receptors - Major circulating catecholamine under basal condition (95% derived from peripheral sympathetic nerve endings, remainder from adrenal medulla) * *2) Adrenaline** - β1 and β2 receptors, weak actions at α1 receptors - All secreted from adrenal medulla * *3) Dopamine** - Released during intense adrenal medullary activity (under severe stress) - most of the circulating dopamine is of renal origin

Answer 64

**- Phaeochromocytoma (mainly this in adults)** - Neuroblastoma (in \<4yo) - Ganglioneuroma - Sympathoblastoma

Answer 65

NO LONGER VALID! - 10% in children - 10% bilateral - 10% multiple - 20% extra adrenal - 24% familial (e.g. MEN2) - 36% malignant

Answer 66

20% of pheochromocytoma are extra-adrenal: * *Site**: - organ of Zuckerkandl, located at the aortic bifurcation - sympathetic chain - thorax - urinary bladder, scrotum **Note**: Extra-adrenal tumours tend to produce **noradrenaline only** whereas adrenal tumours usually produce both adrenaline and noradrenaline

Answer 67

_**P**aroxysms of **4Ps** & others:_ 1) Hypertension (**pressure**) - episodic or sustained 2) Sever pounding Headache (**pain**) 3) Hyperhidrosis aja diaphoresis (**pespiration**) 4) **Palpitation**, tachycardia, angina 5) Flushing 6) Anxiety, feeling of impending doom 7) Weight loss, hypermetabolism, pyrexia (if very severe) 8) Hyperglycaemia, hyperlipidemia, hypokalemia 9) Complications, e.g. - stroke - heart faillure - hypertensive encephalopathy

Answer 68

_LAB TESTS:_ * *1) 24 hour urine for** - urine catecholamines and break down products, e.g. - vanillylmandelic acid (VMA) - metanephrine, normetanephrine * *2) Plasma catecholamines** - Plasma noradrenaline & adrenaline - can help determining whether it is adrenal or extra-adrenal, as extra-adrenal cannot produce adrenaline _LOCALISATION by RADIOLOGY_ **3) Adrenal CT scan / MRI** * *4) Meta-iodo-benzyl guanidine (MIBG) scan** - radioactive iodine labelled MIBG will be taken up by chromaffin tissues

Answer 69

Contrast injection may induce a pressor crisis and patients should be prepared with complete adrenoceptor blockade

Answer 70

* *1) Screening for MEN2** - Blood x CaPO4, PTH, Calcitonin, CEA - thyroid USG +/- FNAC **2) Surgical resection** (e.g. adrenalectomy) is the only treatment: * pre-op: - full alpha and beta blockade to prevent hypertensive crisis - start with alpha blockage for BP control, 14 days pre-op (Phenoxy-benzamine) - followed by beta blockage for HR control, 3 days pre-op (Propanolol) * Intra-op - early ligation of venous drainage - minimal manipulation

Answer 71

α blocker (phenoxybenzamine) first, followed by β blocker (propanolol). α is for BP control, β is to reduce tachycardia. If β blocker administered first, vasoconstriction due to unopposed α adrenoceptor activity may occur and exacerbate hypertension (normally beta 2 for vasodilation -\> if blocked then vasoconstriction too)

Answer 72

**0) Admit to ICU, ABC etc** **1) Volume repletion with NS** * *2) IV Phentolamine** 0.5-5mg (alpha blockade) - then phentolamine infusion, or - then nitroprusside infusion * *3) Beta-blocker** - Propanolol if tachycardia (ensure adequate alpha-blockade by phentolamine) - Labetalol infusion

Answer 73

- kidney juxtaglomerular cells produced Renin - liver produced angiotensinogen - Renin converts angiotensinogen to angiotensin I - angiotensin I is converted by lungs' ACE to angiotensin II - Angiotensin II increases growth & vascularity of zona glomerulosa, increases aldosterone synthesis

Answer 74

**1) Renin‐angiotensin‐aldosterone system** juxtaglomerular cells increases renin when: - decreased perfusion pressure (i.e. low BP, dehydration) - decreased NaCl delivered to macula densa - increase sympathetic stimulation * *2) Na & K** - Hyponatremia & hyperkalemia increase aldosterone secretion - Hypernatremia would decrease aldosterone secretion * *3) ACTH, exercise, erect posture** - short term stimulation (negligible effects) * *4) Atrial natriuretic peptide ANP** - if volume overload, ANP will be released by atria in response to high BP, decreasing aldosterone secretion * *5) Age** - older age will also decrease aldosterone secretion

Answer 75

**Increase Na and water reabsorption** at ascending loop of Henle & distal convoluted tubules by: 1) Increase Na channel & Na/K ATPase insertion 2) Enhances H⁺ & K⁺ excretion (by upregulation of K channel & H channel)

Answer 76

* *1) Secondary Hypertension (due to fluid retention)** - usually diastolic hypertension - HTN complications e.g. headache, CAD, CHF, retinopathy * *2) HypoK** - _Polydipsia, polyuria_, nocturia - Weakness, flaccid paralysis, latent tetany - Parasthesiae (of UL & LL)

Answer 77

* *_PRIMARY HYPERALDOSTERONISM_ 1) Adrenal adenoma** (most common) - "aldosterone producing adrenal adenoma" (APA) * *2) Adrenal hyperplasia** - almost always bilateral, i.e. Idiopathic bilateral adrenal hyperplasia (IHA) * *3) Adrenal carcinoma** - rare * *4) Dexamethasone -suppressible hyperaldosteronism** - a familial disease, very rare in Chinese **_SECONDARY HYPERALDOSTERONISM_** Due to renin over-production by JXG cells: **1) Renal artery stenosis** * *2) Congestive heart failure, nephrotic syndrome, cirrhosis** - reduced renal perfusion activates the RAAS * *3) Juxtaglomerular cell tumour** - very rare

Answer 78

* *1) Site** - adrenal adenoma is usu unilateral - adrenal hyperplasia is almost always bilateral * *2) Physiology** - Adenoma is very sensitive to ACTH - Hyperplasia responds excessively to angiotensin II but not to ACTH * *3) Biochemical assays** - Plasma K (low), basal serum aldosterone (high), basal PRA (plasma renin activity, low) - Biochemical disturbances are more severe in Adrenal adenoma, and less severe in hyperplasia * *4) Adrenal venous sampleing** for aldosterone level - adenoma is unilaterally increased aldosterone, contralaterally repressed - hyperplasia is bilaterally increased aldosterone * *5) Postural test** (from supine to erect) - adenoma will not show a rise in aldosterone - hyperplasia will show an exaggerated rise in aldosterone * *6) Imaging** - CT, MRI adrenals, and Iodocholesterol scanning will show: - unilateral if adenoma - bilateral if hyperplasia

Answer 79

First ensure _normal dietary Na intake_ & _cessation of drugs_ e.g. diuretics, β-blocker, ACEI, ARB: **1) Exclude other causes of K loss** from Hx (e.g. diuretics, GI loss, renal tubular acidosis) * *2) RFT, electrolyte panel, urine K** - Hypokalemia - Inappropriate kaliuresis (\>30/day) * *3) Spot Aldosterone, Renin** - Aldosterone Renin Ratio \>30 = likely primary hyperaldosteronism _{Definitive diagnosis of Primary hyperald:} * *4) Salt loading test (****Saline infusion test)** - rule out Heart failure before start - 0.9% normal saline iv (500 ml/h) for 4 hours - Monitor pulse and BP and watch out for signs of fluid overload - Measure renin & aldosterone post salt loading - Normally aldosterone should decrease; if aldosterone remains high, then hyperaldosteronism

Answer 80

_For adrenal adenoma or carcinoma -\> surgical therapy_ * *1) Lap adrenalectomy** - Pre-op spironolactone and K supplement for 2-3 weeks to correct HTN _For adrenal hyperplasia -\> medical therapy if bilateral_ * *1) Aldosterone antagonists** - Spironolactone (note gynaecomastia) - Eplerenone (expensive) **+/-2) Lap adrenalectomy** if unilateral hyperplasia

Answer 81

BBIIG **1) Blood pressure maintenance** (up regulation of alpha adrenoceptor on arterioles) -\> INCREASE BP * *2) Reduce Bone & connective tissue formation** - Inhibits osteoblasts & protein synthesis, stimulates PTH for bone resorption - Inhibits fibroblast proliferation & collagen formation (thus striae) **3) Immunosuppression & anti-inflammatory** **4) Insulin resistance** **5) Glucose increase** by gluconeogenesis, glycogenolysis, reduced glucose uptake **6) Mobilize protein** (proteolysis) from non-hepatic tissues to liver for protein genesis **7) Fat** : increase lipolysis, decreased lipogenesis **8) Hypokalemia** -\> weak muscle

Answer 82

* *1. Hypothalamic‐pituitary‐adrenal axis** - paraventricular nucleus releases CRF -\> anterior pituitary release ACTH -\> cortisol from adrenal cortex * *2. Diurnal rhythm** - Diurnal rhythm of CRH, and thus ACTH & cortisol - Cortisol high in the morning, low in late afternoon & at night - Under control of suprachiasmatic nucleus SCN * *3. Negative feedback** - Long loop: Negative feedback of plasma cortisol on hypothalamic CRF & pituitary ACTH production - Short loop: plasma ACTH on CRF secretion **4. Stress** increases CRH, ACTH & cortisol

Answer 83

* *1) Truncal obesity** - Moon face - Buffalo hump - interscapular & supraclavicular fat pads * *2) Proximal muscle wasting & weakness 3) Osteoporosis** * *4) Skin changes** - acne vulgaris - thin skin - excessive bruising - purple (violaceous) abdominal striae - hirsutism, hyperpigmentation if pituitary cause (i.e. Cushing's disease) **5) Hypertension, hyperglycaemia** (DM) * *6) Hypogonadism** - impotence, decreased libido - if pituitary type, then hirsutism in women **7) Increased likelihood of infection e.g. fungal infection** **8) Psychiatric disturbances** - non-specific, depression, euphoria, frank psychosis \_\_\_\_ plus side effects of exogenous steroids in iatrogenic Cushing's: 9) avascular necrosis of femoral head 10) cataract in iatrogenic Cushing's

Answer 84

* *1) Iatrogenic Cushing syndrome (ACTH independent)** - most common - no hyperpigmentation - no androgen excess (i.e. hirsutism in female) as exogenous steroids suppress adrenal androgen production - may present with avascular necrosis & cataract * *2) Cushing's Disease (ACTH dependent)** - i.e. ACTH secreting pituitary adenoma, causing bilateral adrenal hyperplasia - Note hyperpigmentation and androgen excess **3) Adrenal adenoma or carcinoma (ACTH independent)** * *4) Ectopic ACTH production (ACTH dependent)** - lung small cell carcinoma - carcinoid - CA pancreas - thymoma

Answer 85

_SCREENING for Cushing Syndrome_ * *1) 1mg ONDST** - PO 1mg dexamethasone at 11pm, recheck cortisol 9am next day - if cortisol not suppressed, then likely Cushing's * *2) Low dose Dexamethasone Suppression Test** - more specific, can rule out pseudo-Cushing state - 0.5 mg q6h x 2/7 _CAUSE DETERMINE (for Cushing disease)_ * *3) High dose dexamethasone suppression test** - 2mg q6h for 2 days, then check cortisol and ACTH - High dose steroid should suppress pituitary over-secretion in Cushing's disease (as still retain some negative feedback) - However unable to suppress adrenal Cushing's * *4) CRH stimulation test** - IV injection of 1 ug/kg CRH - look for cortisol and ACTH level - if cortisol/ACTH level increased, then Cushing disease _RADIOLOGY & OTHERS:_ **5) MRI pituitary, CT Adrenals** **6) CXR** - look for small cell lung cancer, thymoma **7) Venous & inferior petrosal sinus sampling for ACTH**

Answer 86

* *Healthy:** - normal ACTH, normal cortisol - corticol suppression in low & high dose Dex Sup Test - cortisol increased in CRH Sti Test * *Cushing's Disease** - high ACTH, high cortisol - No suppression in low dose Dex Sup Test - cortisol suppression (\>50%) in high dose Dex Sup Test - cortisol increased in CRH Sti Test * *Adrenal hyperplasia/adenoma** - low ACTH, high cortisol - No suppression in low dose Dex Sup Test - No suppression (\<50%) in high dose Dex Sup Test - No increase in CRH Sti Test * *Ectopic ACTH secretion** - high ACTH, high cortisol - No suppression in low dose Dex Sup Test - No suppression (\<50%) in high dose Dex Sup Test - No increase in CRH Sti Test

Answer 87

* *1) Iatrogenic Cushing** - tapering down of steroids * *2) Cushing Disease** - transphenoidal resection of pituitary adenoma * *3) Adrenal hyperplasia or adenoma** - lap adrenalectomy - with peri- & post-op glucocorticoid replacement * *4) Ectopic ACTH production** (malignancy) - treat secreting lesion: surgical excision, chemo, radi

Answer 88

_PRE-OP_ * *1) Medical treatment to reduce risk of morbidity (e.g. infection)** - Metyrapone (1st line), blocks 11β -hydroxylase to stop cortisol synthesis - Ketoconazole, which inhibits cortisol & androgen * *2) Correct metabolic problems** - HTN - DM - hypokalemia **3) Prophylactic antibiotics** _POST-OP_ * *4) Post-op steroid cover** - once source of high ACTH removed in pituitary Cushing’s , there might be sudden low cortisol level because of lack of response of HPA axis at stress * *5) Peri-operative heparin** (esp Caucasian) - as DVT prophylaxis - due to hypercoagulability in white Cushing patient

Answer 89

**"GP FLAT"** * *1) GH Growth Hormone 2) Prolactin** * *3) FSH Follicle Stimulating Hormone 4) LH Luteinizing Hormone** * *5) ACTH Adrenocorticotropic hormone 6) TSH Thyroid stimulating hormone** * 7) Beta endorphin 8) Lipotropin 9) MSH Melanocyte stimulating hormone*

Answer 90

1) Anti Diuretic Hormone (ADH) 2) Oxytocin

Answer 91

From **Internal carotid artery**: 1) Right and left superior hypophyseal arteries -\> forms primary capillary plexus (supply median eminence and infundibulum) -\> form veins and secondary capillary plexus in adenohypophysis (\*\*hypophyseal portal system) 2) Right and left inferior hypophyseal arteries -\> supplies neurohypophysis and a small supply to infundibulum =\> hypophyseal veins

Answer 92

- GnRH (=\> LH FSH) - CRH (Corticotropin-releasing hormone) =\> ACTH, MSH, beta endorphin - Thyrotropin-releasing hormone (TRH) =\> TSH & Prolactin - GHRH =\> GH - Somatostatin =\> decrease GH, TSH, prolactin - Dopamine =\> decrease prolactin

Answer 93

1) Binds to adrenal cortex membrane receptor that activates adenylate cyclase, increase cAMP, increase PKA 2) Stimulates the synthesis & secretion of mainly cortisol from the zona fasciculata of adrenal cortex (aldosterone mainly controlled by renin-angiotensin system)

Answer 94

1) In female: Development of Graffian follicles -\> Oestrogen production (for proliferative phase of endometrium & secondary sexual characteristics) 2) male: spermatogenesis

Answer 95

1) female: causes ovulation and maintains the corpus luteum, to produce Progesterone (Secretory phase of endometrium for implantation) 2) male: stimulate Leydig cell to produce testosterone (secondary sexual characteristic)

Answer 96

* *A) INDIRECT ACTION** 1) causes liver to produce somatomedins/ insulin like growth factors (IGF), which ↑ glucose uptake and ↓ lipolysis initially 2) somatomedin stimulate bone growth at epiphysis of long bones - increases deposition of protein by chondrocytic & osteogenic cells - increases the proliferation of chondrocytic & osteogenic cells - promotes conversion of chondrocytes into osteogenic cells * *B) DIRECT ACTION** 3) Promotes protein synthesis, decrease proteolysis 4) Enhances fat utilization for energy (enhance lipolysis and beta oxidation) 5) Decreases carbohydrate utilization; After a few hours: insulin antagonistic effect to ↓ glucose uptake and ↑ lipolysis; increased gluconeogenesis in liver

Answer 97

1) stimulates V1 receptor on vascular smooth muscle to cause vasoconstriction to ↑ blood pressure 2) stimulates V2 receptor on distal and collecting ducts to increases water reabsorption by insertion of aquaporin 2

Answer 98

Effect on milk ejection (letdown reflex) - causes contraction of the myoepithelium of the breast Effect on the uterus - causes contraction in parturition (baby delivery)

Answer 99

_In Women_ * *1) Oligomenorrhoea, amenorrhoea 2) Anovulatory subfertility** * *3) Decreased libido, dyspareunia, vaginal dryness** **4) Galactorrhoea** **5) Risk of osteoporosis** * *6) Parasellar signs & symptoms** (if pituitary cause) - headache, papilloedema, early optic atrophy (RAPD) - bitemporal hemianopia _In Men_ * *1) Hypogonadotrophic hypogonadism** (testicular atrophy, loss of pubic, leg hairs or axillary hair, less facial hair) - \> because high prolactin reduces GnRH in hypothalamus, thus lower LH & FSH, thus lower estrogen or testosterone **2) Decreased libido, impotence, no nocturnal penile tumescence** **3) Parasellar signs and symptoms** (e.g. visual field defects and headaches) *4) Galactorrhoea or gynecomastia (rather uncommon)*

Answer 100

- Classical teaching is "**uncommonly**", as gynecomastia is a estrogenic effect. - However, it is possible to see gynaecomastia in ~30% of male hyperprolactinaemia, because: 1) Prolactin can reduce gonadotrophin, causing **secondary hypogonadism** 2) adrenal cortex continue to produce estrogen precursor, thus gynaecomastia

Answer 101

_Physiological_ **0) Pregnancy, Lactation** _Pathological_ **1) Prolactinoma (pituitary adenoma)** * *2) Suprasellar mass lesion** - when tumour compresses hypothalamus or pituitary stalk -\> reduced tonic dopamine secretion or delivery to anterior pituitary -\> thus cannot inhibit prolactin secretion * *3) Hypothyroidism** - reduced T4, thus increase TRH in hypothalamus, which stimulates pituitary TSH & prolactin * *4) Iatrogenic from drugs** - Anti-psychotics e.g. clozapine, chlorpromazine, haloperidol (dopamine receptor blocker) - Methyldopa (anti-hypertension, which reduces dopamine synthesis) - Metoclopramide (anti-emetic) - Estrogen in COC pills (by increasing prolactin secreting cells) * *5) Chronic renal failure** - impaired dopamine action - reduced prolactin clearance * *6) Chestwall lesions e.g. trauma, Herpes zoster** - intercostal nerve irritation might stimulate letdown reflex

Answer 102

**1) Pregnancy test** if reproductive age woman * *2) Serum non-stressed prolactin level** - if \>3 times of upper limit, suggestive of prolactinoma - if \>10 times of upper limit, almost certainly prolactinoma **3) MRI pituitary** to look for prolactinoma * *4) Screen for other pituitary enzymes** - IGF-1 level - FSH LH - 9am ACTH, 9am cortisol - Thyroid function test (fT4, TSH)

Answer 103

* *1) Dopamine agonist** - bromocriptine or cabergoline * *2) Trans-sphenoidal surgical resection** - if drug intolerance, resistance, incompliance * *3) Pituitary radiotherapy** - as an alternative if medical & surgical therapy failed, refused or contraindicated - consider prior to pregnancy in a patient with poor compliance to follow-up * *4) Continued monitoring & FU** - for development of hypopituitarism after treatment

Answer 104

_Surgery_ + Quick correction of hyperprolactinemia - GA & surgical risk - risk of post-operative DI - risk of cerebrospinal fluid leakage - risk of hypopituitarism - recurrence of macroadenoma _Radiotherapy_ + Less short term risk - higher risk of hypopituitaryism in the long term - years of delay before normalization of hyper-prolactinemia

Answer 105

0) If children, **gigantism** will occur as epiphyseal plates of long bones are not closed _Acromegaly in adults:_ * *1) Overgrowth facial features** - coarsing of facial features - prominent supraorbital ridges, large nose, prognthism - thick lips, increased interdental separation - macroglossia, OSA - deeper voice * *2) Overgrowth of MSS** - Sweaty palms, oily skin - "spade hands", "spatula fingers" (ask ring size) - large feet, thick heel pad (ask shoe size) - osteoarthritis - arthralgia from joint tissue overgrowth, kyphosis, carpal tunnel syndrome - proximal myopathy * *3) Visceral overgrowth (organomegaly)** - Goitre - Cardiomyopathy, LV hypertrophy - Hepatomegaly - Prostatic hypertrophy - Uterine fibroids (menorrhagia?) - Colorectal polyps & cancer (PR bleed?) * *4) Metabolic disturbances** - Hypertension - impaired glucose tolerance, DM (glycosuria in PE!!!) - Hypertrichosis, gynaecomastia * *±5) Parasellar symptoms & signs (if pituitary adenoma)** - raised ICP, headache, papilloedema - bitemporal hemianopia; optic atrophy - opthalmoplegia from cavernous sinus syndrome (if lateral)

Answer 106

* _A. Due to tissue overgrowth:_* * *1) OSA 2) Cardiomyopathy, LV hypertrophy** * *3) Joint pain, kyphosis, carpal tunnel syndrome 4) Uterine leiomyoma 5) Colonic polyps, CRC** * _B. Metabolic derangements:_* * *1) Hypertension, LV hypertrophy 2) Glucose intolerance & DM** * _C. Parasellar Cx:_* * *1) Raised ICP 2) Bitemporal hemianopia, optic atrophy, cavernous sinus syndrome, CN palsies**

Answer 107

Mortality = 2-3x the expected rate due to: * *1) Cardiovascular disease** - HOCM - increased atherosclerosis from dyslipidemia, HTN, DM **2) Colorectal Cancer & other cancers**

Answer 108

_*\*\* Random GH level is not useful as GH level fluctuates*_ **1) Elevated serum IGF-1** (aka somatomedin C) * *2) Oral glucose suppression test** - glucose load normally should suppress GH - in acromegaly, GH is not suppressed by glucose load * *3) Pituitary MRI** - for adenoma * *4) Screen for other pituitary enzymes** - serum prolactin - FSH LH testosterone - 9am ACTH, 9am cortisol - Thyroid function test (fT4, TSH) _later_ **±5) Colonoscopy** to look for polyps or cancer

Answer 109

**1) Trans-sphenoidal resection** of pituitary adenoma * *2) Post-op radiation therapy** - esp if IGF-1 level remain elevated _Medical therapy:_ * *3) Somatostatin analog** - IM Octreotide (long acting) every 4 weeks - IV Pasireotide daily might be useful * *4) GH receptor antagonist** - Pegvisomant (daily injection) * **+5)*** ***Dopamine agonists*** - i.e. *Bromocriptine and Carbegoline PO - * helpful in ablating the mass and normalising IGF-1 level

Answer 110

Usually _GH FSH LH_ are lost first, before _ACTH TSH_; * *1) Reduced GH:** - growth failure in children - decrease muscle mass in adults - increase LDL, CVS disease, weight gain - osteoporosis, fatigue * *2) Reduced prolactin:** - cannot lactate * *3) Reduced FSH, LH** - hypogonadotrophic hypogonadism - subfertility, low libido, amenorrhoea, osteoporosis * *4) Reduced ACTH:** - secondary adrenal insufficiency (glucocorticoid only) - weakness, fatigue, anorexia, orthostatic hypotension, nausea, vomiting - hypoNa - No salt craving or hyperK (unlike primary adrenal insufficiency, which aldosterone is involved too) - often asymptomatic until unmasked as Addisonian crisis by stress * *5) Reduced MSH:** - decreased skin and hair pigmentation i.e. "Alabaster skin" * *6) Reduced TSH:** - secondary hypothyroidism * *7) Local mass effect** of pituitary lesion causing parasellar symptoms - headache, bitemporal hemianopia **±8) Diabetes insipidus (if hypothalamic or stalk disease)**

Answer 111

_A. Pituitary causes (primary)_ * *1) Non-functional pituitary macroadenoma 2) Brain metastatic tumour** * *3) Pituitary apoplexy 4) Non-haemorrhagic infarction (stroke)** - Sheehan's syndrome (post partum haemorrhage) - cavernous sinus thrombosis, carotid aneurysm * *5) Trauma** - midline skull fracture in RTA, head injury * *6) Iatrogenic** - intracranial surgery - post irradiation (e.g. NPC radiotherapy) * *7) Infection hypophysitis** (TB, toxoplasmosis in HIV) * *8) Autoimmune hypophysitis** aka lymphocytic hypophysitis * *9) Infiltration** (haemochromatosis e.g. haemosiderosis in Thal transfusion, sarcoidosis) _B. Hypothalamus lesions_ - note DI (reduced ADH) and increased prolactin (due to decreased dopamine in this case) * *1) Tumours** e.g. craniopharyngioma * *2) Infection 3) Surgery, radiation 4) Trauma 5) Infiltration**

Answer 112

* *1) Pituitary apoplexy** - bleeding or infarct of pituitary tumour * *2) Non-haemorrhagic infarction** of pituitary gland from: - catastrophic obstetric haemorrhage (Sheehan’s syndrome) - diabetes mellitus - raised intracranial pressure

Answer 113

* *1) GH deficiency** - replacement in adults is controversial - daily SC injection of GH for children * *2) Gonadotrophin deficiency** - Testosterone replacement - Estrogen replacement with Progestogen (prevent malignancy) - For women fertility induction, give recombinant FSH/LH, or HMG (human menopausal gonadotrophin) or HCG (human chorionic gonadotrophin) * *3) ACTH deficiency** - prednisone, or hydrocortisone (fludrocortisone is only needed in primary adrenal insufficiency, NOT secondary cortisol insufficiency) * *4) TSH deiciency** - Levothyroxine replacement

Answer 114

Must **replace cortisol first**, before replacement of thyroxine: - if thyroxine replaced first, the increased metabolic rate will precipitate an Addisonian crisis with abnormal cortisol axis

Answer 115

1) Acute pan-hypopituitarusm e.g. Addisonian crisis 2) Acute onset of headache (retroorbital or temporal) 3) Symptoms of raised ICP e.g. nausea & vomiting 4) Meningeal irritation sometimes e.g. neck rigidity 5) Bitemporal hemianopia (optic chiasm lesion) 6) Diplopia from CN III (or sometimes IV, VI) compression @ cavernous sinus 7) Sometimes even stroke due to carotid artery compression @ cavernous sinus

Answer 116

* *Diagnosis** - definite Dx based on CT or MRI * *Management:** 1) Surgical decompression under steroid cover if - raised ICP - altered consciousness - compression on neighbouring structures 2) Replace pituitary hormones