Endocrine Surgery Flashcards

Question 1

Q

Explain thyroid physiology

(Axis and feedback)

Answer

A

1) Hypothalamus releases TRH (thyrotrophin releasing hormone)
2) Anterior pituitary stimulated by TRH to release TSH (thyroid stimulating hormone)
3) Thyroid gland stimulated by TSH to release T3 & T4 (triiodothyronine and tetraiodothyronine)

i. Negative feedback loop: circulation T3/T4 inhibit TRH & TSH secretion

ii. Environmental factors: Cold, trauma, stress
iii. Excessive iodide (anti-TSH) inhibits T3 T4

Question 2

Q

Thyroid hormone biosynthesis

Answer

A

*1) Iodide trapping
2) Oxidation
3) Iodination/Organification
4) Coupling**
1) iodide is taken up actively by Na-I symporter (activated by TSH/cAMP)

2) iodide is oxidized by thyroidal peroxidase to iodine in thyroglobulin
3) tyrosine residue in thyroglobulin is iodinated and forms MIT (monoiodotyrosine) & DIT (diiodotyrosine).
4) iodotyrosines (MIT & DIT) are coupled together to form T3 & T4 [MIT+DIT=T3; DIT+DIT=T4]

Question 3

Q

Physiological effects of Thyroid hormone

Answer

A

*BBBBBP**
1) Bone growth and growth
2) Brain maturation and CNS effect
3) Basal metabolic rate and thermogenesis
4) Beta-adrenergic effects and enhance heart contraction
5) Biphasic Metabolism modulation
6) Permissive effect on other hormones

Question 4

Q

What blood tests to consider in thyroid disease

Answer

A

1) Thyroid function test:

TSH
fT4
fT3

2) Antibodies (usu not needed)

TSH receptor antibody (TRAb): this may stimulate or inhibit thyroid TSH receptors; the former is the case in Graves’ disease
Thyroid peroxidase antibody (TPOAb): elevated in Graves’ disease and thyroiditis; lacks sensitivity and specificity for the former
Thyroglobulin antibody (TgAb): elevated in Hashimoto’s disease and Graves’ disease; highly sensitive in the former

3) Calcium profile
- to look for associated parathyroid issue

4) Thyroglobulin
- if suspicious of thyroid cancer

Question 5

Q

Why is TSH the most valuable parameter in TFT?

What are the pre-requisites of using it.

Answer

A

Because TSH is the most sensitive:

inverse log relationship with T4
i.e. small change in fT4 will cause large response in TSH
thus in early thyroid disease, TSH change will precede fT4 level change

Pre-requisites of using ONLY TSH to screen:

assuming intact H-P axis (i.e. when not worrying about pituitary or hypothalamic causes)
assuming stable thyroid status (i.e. no recent therapy for thyroid condition)

Question 6

Q

Which hormone levels are a more accurate reflection of thyroid function status?

Answer

A

The majority of circulating thyroid hormones are bound to serum proteins (thyroxine-binding globulin and albumin). Protein-bound T3 and T4are considered inactive. Changes in binding protein concentrations occur in a number of conditions and can impact the total thyroid hormone concentrations.

Free T3 and T4 are considered biologically active and are therefore a more accurate reflection of thyroid function status

Question 7

Q

Why is T3 not measured, or of use, in hypothyroidism?

Answer

A

T3 levels are sensitive to medications such as amiodarone, phenytoin and salicylates.

They are also variable in a range of physiological states such as pregnancy and sepsis

Question 8

Q

Interpret the following thyroid function profiles:

1) Low TSH, high fT4
2) Very low TSH, normal fT4
3) Low TSH, normal fT4
4) High TSH, low fT4
5) Normal/low/undetectable TSH, low fT4
6) High TSH, normal fT3

Answer

A

*1) Undetectable/very low TSH, high fT4:**
Primary Hyperthyroidism
*2) Very low TSH, normal fT4**
Mild hyperthyroidism
*3) Low TSH, normal fT4**
Subclinical hyperthyroidism
*4) High TSH, low fT4**
Primary hypothyroidism
*5) Normal/low/undetectable TSH, low fT4**
Secondary hypothyroidism (pituitary / hypothalamic)
*6) High TSH, normal fT3**
Subclinical hypothyroidism

Question 9

Q

Causes of thyrotoxicosis

Answer

A

Thyroid pathology:

*1) Graves disease** aka diffuse toxic goitre (80%)
*2) Plummer disease** aka toxic MNG (15%)
*3) Toxic thyroid adenoma** (~2%)
*4) Initial phase of Thyroiditis** (hyperthyroidism should be transient, as it is release of pre-formed TH)
i) Hashitoxicosis
ii) subacute thyroiditis
iii) post partum thyroiditis

Other causes:
5) Pituitary hyperthyroidism e.g. TSH-secreting pituitary adenoma (note visual field defect)

*6) Iatrogenic, iodide induced** (Jod Basedow effect)
i) Amiodarone (~3%, esp in iodine deficient patients)
ii) Iodine containing contrast agents
iii) Levothyroxine overdose (Thyrotoxicosis factitia)
*7) Mimicry from high HCG**
i) Molar hyperthyroidism
ii) Germ cell tumour

8) Extrathyroidal TH production in struma ovarii (very rare kind of ovarian tumour)

Question 10

Q

Clinical manifestation of hyperthyroidism

Answer

A

0) might be a goitre

General:

*1) Weight loss**; increased appetite; heat intolerance, hyperhidrosis
*2) Hand tremor**, nervousness, irritability, hyperactive
*3) Insomnia, fatigue**

MSS:

*4) Skin changes**: palmar erythema, alopecia, warm and moist skin, (pretibial myxedema & thyroid acropachy aka clubbing in Graves’)
*5) Proximal myopathy**; Periodic paralysis (esp in chinese)
*6) Osteoporosis**

Systems:

*7) Eye signs**
All: lid retraction, lid lag
Graves’: periorbital oedema, conjunctival irritation, exopthalmos, diplopia from extraocular muscle involvement)
*8) Palpitation**
sinus tachycardia
atrial fib
PVC -> HTN & HN
*8) Diarrhoea
9) Brisk reflex, hyperreflexia**
*10) Loss of libido, impotence, amoennorhoea, infertility**

Question 11

Q

Graves’ ophthalmopathy Classifications

Answer

A

NO SPECS

0 = No signs or symptoms

I = Only signs (lid lag, retraction) no symptoms

II = Soft tissue involvement (signs and symptoms)

III = Proptosis

IV = Extraocular muscle involvement

V = Corneal involvement

VI = Sight loss from optic nerve involvement

Question 12

Q

What are some immediate complications of thyrotoxicosis?

Answer

A

1) Thyrotoxic heart disease, include AF and heart failure

2) Thyroid storm

Question 13

Q

Mx of Graves’ disease (& hyperthyroidism in general)

Answer

A

*All) Immediate control of heart rate:**
Propanolol (β-blocker)
taper off β-blocker after 4-8 weeks after commencement of methimazole

Then can choose one of three definitive Mx:

*1) Antithyroid drug (Thiouracil derivatives)**
Methimazole is preferred; PTU can be considered in pregnancy
Trial of 1-2 year, may cause remission
Can consider long term

2) Radioactive iodine (RAI) ablation

*3) Surgery**
Total or subtotal thyroidectomy
*±5) Manage Grave’s opthalmopathy**
smoking cessation, eye drops for protection
Selenium supplements if mild
Immunosuppressants esp prednisone
orbital irradiation
orbital decompression surgery

Question 14

Q

What class of medication can you prescribe patients with hyperthyroidism for symptom relief?

Question 15

Q

ADR of thiouracil derivatives (for hyperthyroidism)

📕

Answer

A

Need monitor WCC and LFT

1) Rash

*2) Agranulocytosis** (monitoring of WBC is important!)
fever, sore throat
reversible, usu first 2 months
Common in high dose or old age
*3) Cholestatic jaundice**, Hepatocellular toxicity (rare)
monitoring of LFT, esp first 6 months
*4) Acute arthalgia**, ANCA induced vasculitis (rare)
more in long term PTU
*5) Teratogenesis** (aplasia cutis, choanal atresia)
PTU less so

Question 16

Q

Contra-indications of 131-I Radioactive Iodine (RAI) treatment

Answer

A

1) Pregnancy
2) Moderate or severe orbitopathy in Grave’s disease (will cause exacerbation)

Question 17

Q

Indication for surgical therapy of Grave’s disease

Answer

A

1) Suspicious of malignancy
2) Large goitre (>80g), esp with obstructive symptoms
3) Co-existing hyperPTH for same session OT
4) Persistent hyperthyroidism despite medical treatment and failed RAI
5) Moderate to severe Graves’ ophthalmopathy
6) Pregnant ladies who are intolerant of anti-thyroid drug

Question 18

Q

Preoperative preparation for thyroidectomy (& reason)

Answer

A

1) Antithyroid drug therapy until euthyroid
2) β-blocker for two weeks
3) Lugol’s solution

*Rationale**:
stunt the thyroid to make it less vascular before surgery
hyperthyroidism increases surgical risk
reduce risk of thyroid storm after surgery

Question 19

Q

What are the DDx of retrosternal mass

Answer

A

1) Retrosternal goitre (thyroid)
2) Thymoma
3) Teratoma, other germ cell tumour
4) Lymphoma
5) Mediastinal cysts e.g. bronchogenic cyst

Question 20

Q

What are complications of large goitre?

Answer

A

Pressure symptoms, thus causing:

1) Dyspnoea, upper airway obstruction (trachea)
2) Dysphagia (esophagus)
3) Hoarseness (RLN palsy)
4) Horner’s syndrome (Sympathetic ganglion)
5) Jugular vein compression & thrombosis
6) Cerebrovascular steal syndrome

Question 21

Q

Clinical features of hypothyroidism

Answer

A

0) Goitre

General:

*1) Weight gain** with reduced appetite
*2) Cold intolerance
3) Lethargy, fatigue**, depression, somnolence, weakness

System:

*4) Bradycardia, pericrdial effusions
5) Constipation
6) Slowing of mental thoughts, slow relaxation of deep tendon reflexes
7) Menorrhagia, infertility**

MSS:
8) Dry skin, coarse hair, alopecia (loss of lateral eye brows “Queen Anne’s sign”)
9) Muscle stiffness, muscle weakness, arthralgia
10) Carpal tunnel syndrome
11) Myxedema (non-pitting edema; in a severe case)
12) Pallor, periorbital puffiness
__________________
Children:
+ Retardation of growth
+ Mental retardation

Neonate:
+ Cretinism (mental retardation)
+ Short stature
+ Hearing problem
+ Deaf mutism
+ Puffy face
+ Protuberant abdomen
+ Umbilical hernia

Question 22

Q

What is a thyroid incidentaloma

Answer

A

Thyroid incidentaloma:

1) Small size (< 1.5cm)
2) Non-palpable thyroid nodule
3) Discovered from neck imaging for unrelated conditions (e.g. USG, CT, MRI, PET-CT)

Question 23

Q

Thyroid mass DDx

Answer

A

*1) Simple goitre**
diffuse simple goitre
multinodular goitre (colloid, haemorrhagic, cystic, complex, hyperplastic, adenomatous)
*2) Toxic goitre** (with thyrotoxicosis)
Graves’ (diffuse)
Plummers’ (multinodular)
*3) Neoplastic goitre**
benign thyroid nodules (e.g. benign follicular adenoma)
malignant i.e. thyroid carcinoma (papillary, follicular, medullary, anaplastic)

4) Thyroiditis

Question 24

Q

Goitre nature and disease correlation

Answer

A

*Graves:**
diffusely enlarged (symmetrical)
Non-tender, soft
Thyroid bruit
*MNG, or Hashimoto:**
Multinodular
Asymmetrical, bumpy, irregular gland
Hashimoto even “rubbery”
*Toxic adenoma:**
Solitary nodule
thyroid gland is otherwise atrophic
*Subacute**:
exquisitely tender
Diffusely enlarged, not always symmetrical

Question 25

Q

Hx & Clinical Features suggestive of malignancy of thyroid nodule

Answer

A

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)

Question 26

Q

Investigations of a thyroid nodule

Answer

A

*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

Question 27

Q

What are the imaging modalities in assessing thyroid disease?

Answer

A

*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

Question 28

Q

Suspicious features on thyroid USG

Answer

A

*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

Question 29

Q

Indications of FNAC thyroid

Answer

A

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

Question 30

Q

Thyroid FNAC Bethesda classifications; which ones are more common?

Answer

A

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

Question 31

Q

Genetic testing for thyroid cancer

Answer

A

Papillary thyroid cancer:

*- BRAF** (papillary thyroid carcinoma)
*- RET-PTC** (papillary thyroid carcinoma)

Medullary thyroid cancer
- RET (associated with MEN2a, 2b)

Question 32

Q

Management of Bethesda Class I

Answer

A

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

Question 33

Q

Management of Betheda Class III or IV

Answer

A

_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

Question 34

Q

Types of thyroid cancers (& spread, prognosis, association)

Answer

A

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

Question 35

Q

Define MEN

Answer

A

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

Question 36

Q

What are the MEN types?

Answer

A

*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)

Question 37

Q

Investigations for thyroid cancer

Answer

A

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

Question 38

Q

Management of papillary / follicular thyroid cancer

Answer

A

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

Question 39

Q

When would we consider completion thyroidectomy?

(in a patient with PTC with hemithyroidectomy done)

Answer

A

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)

Question 40

Q

Management of medullary thyroid carcinoma

Answer

A

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

Question 41

Q

Risk factors of thyroid cancer

Answer

A

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

Question 42

Q

What are the indications for performing a thyroidectomy?

Answer

A

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

Question 43

Q

What are the pre-thyroidectomy workup

Answer

A

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

Question 44

Q

Hemithyroidectomy VS total thyroidectomy

Answer

A

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

Question 45

Q

What incision would you make for thyoidectomy?

What are your landmarks?

Answer

A

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

Question 46

Q

What vessels need to be ligated during thyroidectomy?

Which set of vessels should be ligated first? Why?

Answer

A

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

Question 47

Q

What layers are traversed in thyroidectomy

Answer

A

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

Question 48

Q

Complications of thyroid surgery

Answer

A

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

Question 49

Q

What should be next to the patient’s bedside after thyroidectomy?

Explain the use

Answer

A

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

Question 50

Q

Why post-thyroidectomy haematoma can cause profound upper airway obstruction?

Answer

A

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)

Question 51

Q

Clinical Presentation of Hypocalcaemia

Answer

A

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

Question 52

Q

What are the tetanic signs of hypocalcemia

Answer

A

*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

Question 53

Q

DDx of hypocalcemia

Answer

A

*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

Question 54

Q

Management of symptomatic hypoCa or <2

Answer

A

*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

Question 55

Q

What regulates Serum Ca?

Answer

A

*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)

Question 56

Q

Is the Serum total Ca measurement accurate? How to be more accurate?

Answer

A

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)]

Question 57

Q

Physiology of hormonal regulation of Ca

Answer

A

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)

Question 58

Q

Parathyroid gland blood supply

Answer

A

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

Question 59

Q

Hypercalcemia clinical features

Answer

A

“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

Question 60

Q

DDx of hypercalcemia

Answer

A

*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

Question 61

Q

Interpreting Ca, Phosphate, PTH values

Question 62

Q

What is secondary hyperparathyroidism? What is the etiology?

Answer

A

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

Question 63

Q

What is tertiary hyperparathyroidism

Answer

A

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

Question 64

Q

Ix of hypercalcemia

Answer

A

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 63

A

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 64

A

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

Answer 65

A

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 66

A

*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 67

A

*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 68

A

*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 69

A

*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 70

A

*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 71

A

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 72

A

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 73

A

*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 74

A

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 75

A

Severe hypocalcemia seen after parathyroidectomy for primary hyperPTH

Due to chronically calcium-deprived bone aggressively absorbing calcium

Answer 76

A

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 77

A

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 78

A

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

Answer 79

A

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 80

A

Incidentally discovered adrenal masses usu in CT

Majority are non-functional adrenocortical adenoma.

Answer 81

A

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 82

A

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 83

A

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 84

A

*Dual blood supply**
1) Portal blood in corticomedullary sinuses having previously drained the adrenal cortex

2) Medullary arteries

Answer 85

A

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 86

A

*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 87

A

- Phaeochromocytoma (mainly this in adults)

Neuroblastoma (in <4yo)
Ganglioneuroma
Sympathoblastoma

Answer 88

A

NO LONGER VALID!

10% in children
10% bilateral
10% multiple
20% extra adrenal
24% familial (e.g. MEN2)
36% malignant

Answer 89

A

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 90

A

Paroxysms 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 91

A

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 92

A

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

Answer 93

A

*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 94

A

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 95

A

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 96

A

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 97

A

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 98

A

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 99

A

*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 100

A

*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 101

A

*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 102

A

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 103

A

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 104

A

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 105

A

*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 106

A

*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 107

A

*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 108

A

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 109

A

*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 110

A

*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 111

A

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 112

A

“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 113

A

1) Anti Diuretic Hormone (ADH)
2) Oxytocin

Answer 114

A

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 115

A

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 116

A

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 117

A

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

Answer 118

A

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 119

A

*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 120

A

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 121

A

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 122

A

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 123

A

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 124

A

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 125

A

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 126

A

*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 127

A

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 128

A

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 129

A

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 130

A

Mortality = 2-3x the expected rate due to:

*1) Cardiovascular disease**
HOCM
increased atherosclerosis from dyslipidemia, HTN, DM

2) Colorectal Cancer & other cancers

Answer 131

A

_** 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 132

A

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 133

A

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 134

A

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 135

A

*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 136

A

*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 137

A

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 138

A

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 139

A

*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

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Endocrine Surgery Flashcards

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