Thyroid disease

Unique = only endocrine gland to store product extracellularly

Anatomy.
Embryology - formed from a median anlage and 2 lateral anlagen (origin of C-cells from ultimobranchial
body) from foregut,.grows down as a diverticulum from the tongue, elements may persist (tongue to
pericardium).pyramidal lobe is persistent distal end of the tract (40% incidence, more often on left)
Fascia.
outer layer of deep Cx fascia contains ant. and ext. jugular veins and encloses SCM.
middle layer surrounds strap muscles (incl omohyoid), and is attached to carotid sheath.
visceral layer covers thyroid, trachea, and has attachment to the carotid sheath.
prevertebral fascia invests vertebral bodies and paravertebral muscles.
thyroid attached to trachea each side by "suspensory ligaments" with "lig of Berry"
Strap muscles.
sternohyoid, sternothyroid (to oblique line of thyroid cartilage), thyrohyoid, omohyoid (from scapula,
across post. triangle to central tendon in deep Cx fascia, then to hyoid).
stabilize hyoid and larynx, but are dispensible
innervation - ansa C123
if muscles are divided, it should be done high (level of cricoid) to preserve nerve supply
Veins
often divide AJV during thyroid exposure.
Superior thyroid v, from superior pole to IJV = facial; Middle thyroid v, from lateral aspect into IJV
Inf thyroid v, from lower pole, down in front of tracheaas a plexus into L > R brachiocephalic v

If goitre is substernal, clavicle can act as a torniquet, therefore deliver gland ASAP.
Arteries
Sup thyroid - 1st branch of ECA, descends parallel and superficial to sup. lary. n..
Divides just above gland, into ant. and post. branches. Also gives small branches.
Inf. thyroid - from thyroCx trunk of subclavian. Tortuous course. Approaches post. aspect of gland at
middle and lower 1/3 junction. Divides into branches some distance from gland, gives PT branches (to be
preserved) and a branch that runs with rec. lary. n.
Thyroidea ima -3%, from aorta or brachiocephalic.
Nerves
(a) Sup lary n - branch of X high in neck. Runs down deep and medial to carotid to superior cornu of hyoid,
on middle constrictor. Close to sup thyroid vessels.
Internal branch - sensory above cords
External branch - medial to artery. Motor to cricothyroid (tensor) & cricopharyngeus.
(b) Recurrent laryngeal n. - mixed;
Includes inf. cardiac n.; trach/oesoph. branches (S&M), pharyngeal to inf. constrictor, sensory below vocal
cords
Inf lary n is terminal branch, motor to all but cricothyroid, incl. contral interarytenoid m.
RLn loops under R. subcl or Lig arteriosum, ascends b/w trachea & oesophagus (64% on R and 77% on L).
Most others are lateral to trachea, occasionally ant/lateral ie R is more likely to be anterior to groove.
Passes beneath susp. lig of thyroid to pass under the caudal border of inf. constrictor, through cricothyroid
membrane to enter larynx.
N may branch outside larynx into motor & sensory branches.
Variable relation to inf thyroid art. - b/w 20%; ant. 20%; behind 60% L post>ant, R post=ant relation
0.6% non-recurrent, on right side, relates to abn. right subclavian artery development. S'times partially
recurrent (around inf. thyroid artery)
Lymphatics.
Rich network. Capsular network, some crossover.
3 efferents, superior to mid-jugular nodes; lateral to deep Cx: inf. to pretracheal

"lateral aberrant thyroid" usually found in a LN, & is a met, arising from a primary on same side.
Thyroidectomy.

Indications
Absolute: ?malignancy
airway obstruction
Relative toxic
cosmesis / anxiety
pressure

Positioning
-Under GA, patient is placed in a supine semi-sitting position on the operating table.
-A sandbag is placed under the shoulders, allowing the neck to be hyper-extended, and the occiput is
cushioned on a head-ring.
-Incision is marked, either pre-operatively, or with a loose tie. The incision is 1cm above the clavicles, in a
pre-existing skin crease = Collar incision just past ant border SCM both sides
(?incisions over sternum produce keloids). Skin may be infiltrated with Marcain + adr.
Procedure
-Skin, SC tissues, platysma divided with scalpel. Large veins in sup. layer of fascia are ligated and divided.
-Skin flaps developed by a combination of sharp and blunt dissection. Allis retractors are used to elevate
the flap to facilitate dissection. Veins stay with the superficial layer. Raise to 1-2cm > notch of thyroid
cartilage, lower flap ~ 2cm
-Jowell's self-retaining retractor used to open wound widely.
-Artery forceps applied to the fascia over the strap muscles each side of the midline and lifted up. The
fascia is then divided in the midline, and any small vessels diathermied.
-Strap muscles are then dissected off the gland, and may be divided b/w artery forceps for extra exposure
(divide high to preserve nerve supply).
-Gentle blunt dissection is continued posteriorly b/w gland and carotid sheath, with the gland being rotated
medially. Middle thyroid vein may be found, ligated and divided. (Very rare non-recurrent RLn on right
side is close to middle thyroid v).
-Superior thyroid vessels then defined. Plane developed b/w superior pole and cricothyroid muscle using a
right-angled forcep. Vessels clamped close to gland to avoid damage to the sup. lary. n., double tied with 2-
0 vicryl ties. SLn is usually medial to vessels. Vessels are clamped and divided individually.
-If procedure for Graves, remember pyramidal lobe
-Trachea is then displayed by division of ant. sup. susp. ligament and inf. thyroid veins.
-Inf. pole then dissected, with early identification of the rec. lary. n. in tracheo-oesophageal groove. Inf
portion of the gland freed from n and trachea. Inf thyroid artery branches are divided individually close to
the gland by a capsular dissection method. This method preserves parathyroids with bs. If PT is
devascularised, it should be autotransplanted.
-Rec lary. n. either idendified low down, or as it enters cricothyroid muscle just above cricoid cartilage.
-Gland then rotated further medially, and vascular tissue divided b/w mosquitoes. Bleeding close to the
insertion of the nerve is best controlled by pressure, or by fine vascular sutures.
-Straight arteries clamped over the isthmus, which is divided and oversewn (lobectomy).
-10G suction drain brought out through a separate stab, 3-0 vicryl for straps & platysma. 2-0 prolene
subcuticular suture for skin.
-Parathyroids should be preserved on their blood supply if possible

SUBTOTAL
After mobilization of lobe and identification of the RLn and parathyroids (if possible), artery forceps are
applied to the lateral edge of the thyroid capsule, leaving a cuff of about 1cm. Gland is then divided. The
cut edges are approximated with 3-0 vicryl or 2-0 CCG.

VERY LARGE INTRATHORACIC

Almost all can be removed via cervical incision. Very rarely need median sternotomy.
Key is control of the vessels. Once vessels controlled, gland can be delivered into neck.
Main structure at risk is brachiocephalic vein, although the gland is rarely adherent to it.
If gland cannot be delivered, capsule may be opened and colloid contents removed.
COMPLICATIONS OF THYROID Sx
-Haemorrhage & airway compromise
-RLn injury - right n is more often anteriorly placed than left n, overall < 1% unilat, 5-20% bilat Sx
After injury, cord lies in paramedian position
Injury usually temporary (6-8weeks) - esp if n has been seen through course
In permanent injury, cord gradually adducts to the midline & contralateral cord may hyperadduct across
midline with voice improvement
Repair of RLn is controversial - may lead to cord spasticity due to random re-innervation
If injury is permanent & compensation after 6-12months is poor, consider teflon injection
-SLn injury - external branch supplies cricothyroid muscle. Loss leads to laxness of ipsilateral vc
Hypoparathyroidism - incidence increases with magnitude of the surgery
Permanent hypoPTism after total thyroidectomy - 5-10%
Due to removal or devascularisation of PTs - so advocate ligation close to capsule
If a gland has been inadvertently removed - Frozen to ensure it is not cancer, then reimplant
-Thyroid storm - occurs in thyrotoxic patients who are stressed (infection/Sx) Due to XS T4 & CAs - fever,
tachycardia, obtundation, N&V, Diarrhoea Rx - resuscitation, beta-blockers, steroids, antithyroid drugs,
iodine (blocks release of preformed T4 from thyroid)
-Hypothyroidism ~25% at 10yrs for ttoxicosis
-Recurrent ttoxicosis

Investigations in thyroid disease

TFTs
<< 1% total = physiological free hormone, rest bound to TBG, TBPA, albumin
T3 more active
T4 converted to T3 (35%) + rT3-inactive (40%)
RIA can measure free hormones
TSH most useful
T3 sometimes up alone in "T3 toxicosis"
low T3 and normal or slightly high TSH in "sick euthyroid"

Thyroid scan
I131- transport and organification of I-
Tc - transport only
useful for diffn of - hyperthyroidism (low TSH, incr. iodine uptake) and - thyroiditis (low TSH, low iodine
uptake). shows MNG in clin solitary nodule in 40% (better than US)
substantial limitations in kids main use to demonstrate ectopic thyroid or hot toxic nodule

US
20% nodules are cystic
40% clin solitary nodule are xle
10% Ca have cystic component
Adjunct to FNAC

FNAC
Need LA, sedation, access to experienced thyroid pathologist
sens 85-99%, spec 70-90%
20% indeterminate/suspicious/insufficient
false + < 5% sampling error, lymphoma
false - < 6% Hashimotos, follicular Ca

Indication for Sx
1.Suspicion of cancer
2.Symptoms of pressure / retrosternal spread (bleed can lead to obstruction)
3.Hyperthyroidism
4.Cosmetic deformity
Hypothyroidism
Congenital 75% sporadic dysgenesis, 10% enzyme defects, 5% pituitary dysfunction, 10% transient

Inflammatory thyroid disease.

1. Hashimotos - commonest. Autoimmune (Anti microsomal and thyroglob in 50-90%).
Infiltrate - lymphos and plasma cells. F >> M
enlarged gland, occ + pain. Occ get dysphagia.
Fibrous variant - hard gland. DDx Reidels
Eventually become hypoT4 (most common cause)
Rx - T4 Risk of papillary Ca and lymphoma
Occ need Sx for local symptoms.
2.Subacute (de Quervain's)- uncommon, non-infectious, ?viral, assoc recent URTI, swollen thyroid, fever,
malaise F>M, sometimes no pain, mildly toxic (DDx Graves). Us tender initially, dec at 2/52 firm
gland resolution.
Path granulomatous
High ESR, High n T4 low T4 N, v. low uptake on thyroid scan.
Self limiting. Rx aspirin, steroids.
3. Suppurative - uncommon, G+ve. Us assoc with pyriform sinus fistula.
Tender, erythematous, may be afebrile, septic Rx - Abs+ drainage
4.Reidels - rare. Hard woody mass. Low T4. Inflammation effects surrounds - invasive fibrosis.
May affect only part of gland, No Abs, N TFTs
Occ have fibrosis elsewhere
Local pressure effects, often need Sx.

Thyrotoxicosis.
Aetiology - Grave's kids = 1-5% all cases, 30% all goitres in kids
Toxic MNG
Solitary toxic adenoma
Toxic thyroiditis (Hashitoxicosis)
Less common - inappropriate TSH
subacute thyroiditis
T4 ingestion
I therapy in endemic goitre (Jod-Basedow disease)
Uncommon - thyroid ca
struma ovarii (thyroid tissue in ovarian teratoma)
chorioca / hydatidiform mole

Graves Disease.
AI disease. Associated with organ-specific AI diseases.
Thyroid stimulating immunoglobulins (TSI) - includes LATS and others referred to as TSH-R Abs
Aetiology possibly related to Y. enterocolitica infn, with X-reactive Ab
F:M - 7-10:1. Rare in <3y, inc thereafter, mostly 20-40y
Hx - Nervousness, sweating, heat intolerance, palpn, fatigue, LoW, incr HR, prox myopathy
OE - diffuse goitre, +/- bruit; eye signs; pretibial myxoedema
Eye signs - some due to hyperT4, lid-lag & lid retraction - noninfiltrative, reversible
some infiltrative, due to polysaccharide deposition in orbit, irreversible (exophthalmos)
Skin changes - only in 5-10%. All of these have eye changes. May come on years later
Ix - Free T4 is most useful test Free T3 is hard to measure, therefore measure total T3.
May be high with n T4. TSH low.
If Dx still equivocal, "TRH stimulation test". Get increased TSH in normals, but not in Graves
Treatment
Drugs - Thioureas, thiouracils, methimazole.
Prevent incorporation of trapped I, & the peripheral conversion of T4 to T3
Long-term remission likely if :- small goitre, T3 toxicosis, short duration, absent TRAb.
Problems: 2-6 week latent period

Ses up to 15% = rashes, pruritis, arthralgia, neutropenia (0.5%)

Need to Rx for > 1yr, up to 2-4yrs
Treatment for 1, 2 and 4 years has remission rates of 25%, 50% and 76% respectively. Disaapearance of
goitre correlates with spont remission. - 1/3 will fail med Rx

Radioactive iodine
Preferred in older adol/ adults
Aim to deliver 5-6 mCi to the thyroid gland 24hr after administration
Results in dose to thyroid cells of 70-100Gy with dysfunction or death of most exposed cells
Problems :- 6/52 - 6/12 latent period
ideal dose unknown - incidence of under- & over- treatment
potential mutagenic effects never demonstrated

Surgery
Preop preparation is less important than in adults ? b/c myocardium much more resilient
Options :-
Iodine- 10 drops of Lugol's solution daily for 10 days
transiently blocks release of T4
causes involution of thyroid gland
some effect for thyroid storm
Beta-blockers (propranolol) - Rx of symptoms, treats thyroid storm, prepares patient for Sx.
May be used as a sole agent (initially 40mg q6h for 48 hr prior to Sx) to reduce HR to <100. Last dose
given 1-2 hr prior to surgery. Continued post op , halving dose on day 3,again on day 4, and stopping on
day 5-8.
Appears that use of propranolol reduces Sx blood loss, makes Sx easier.

Principles of surgery :-
Options are - total thyroidectomy
subtotal, 1 or both sides, leaving 4-10g of tissue
Should not ligate both main inf thy arteries (risk of hypoCa)

Major risks :- haemorrhage (0-1%)

RLn palsy (0-5%)
permanent hypocalcaemia(0-0.6%)
Recurrent hyperthyroidism (1-15%)
Hypothyroidism (increases with time, depends on volume of tissue left)

EVALUATION OF A THYROID NODULE

Uncommon in kids. Often = asymm enlargement of one lobe, Hashimotos or enlarged LNs
True nodule of great concern b/c malignant in 25-55%
Hx - duration and time course
local symptoms (dysphagia, pain, voice changes)
systemic symptoms (incr or decr T4, malignancy elsewhere)
place of birth, FHx, neck irradiation (most nodules are adenomas, most cancers are papillary)
Cancer more likely in :- young (<20), male - 30% cancer risk.
- young female - 18% risk
Exam 70% with paillary Ca p/w low cervical LNs. May only need FNA prior to Sx

Diffuse / multinodular goitre.

Physiologic - puberty, pregnancy
Sporadic
Endemic
If prolonged can become nodular.
Sx for local problems, or if dominant nodule may be ca.
Occasionally get thyrotoxicosis

Benign tumours.
-Adenomas, usually follicular, may be functional. 20% hyperfunctional at 6yrs, esp if > 3cm
May bleed. F : M - 6 : 1. Esp 20-60yo
-"papillary adenomas" are considered to be malignant
-"Hurtle cell tumour" - variant of follicular adenoma. Xistic cell appearance- large, Eophilic, pleomorphic.
Ca risk 5 - 6-%

THYROID CANCER
origin - follicular cells
papillary 70% 90% 5ys
mixed P-F
follicular 15% 75%
Hurtle cell variant
undifferentiated 5% 5%
- C-cells - medullary 10% 60%
undifferentiated
other rare types lymphoma
(5%) teratoma
secondary from kidney, lung, breast, melanoma

Cause unknown. Related to irradiation of neck - papillary

Slight increased incidence of follicular ca in areas of endemic goitre
MTC part of MEN2 syndrome.

Staging

T1 < 1cm N1a ipsilateral

T2 1-4cm 1b other
T3 > 4cm
T4 extrathyroid

Papillary.
solitary nodule in young adult
Spread - lymphatic spread within, then beyond gland.
often p/w palpable Lns - 20% adults, 80% kids
Spreads to lung and bone. Pulm mets more frequent in kids 10% at Dx
Path - Psammoma bodies= laminated Ca2+ spherules in 60%, large cells with orphan Annie nuclei, not
seen on FS. May be mixed pap/follicular,
may be TSH snsitive.
Small papillary carcinomas in 10% at post-mortem - "minimal tumours"
Multifocality common - 30-87% (10% Rxed with <thyroidectomy get local recurrence)
Rx - >1.5 cm total + ND
< 1.5 cm no survival adv to total T
nodes MRND vs pick - ECS very rare, address level VI nodes
spare functional RLN even if encased in tumour.
Adv of total is interpretation of 131I scan given inc pulm mets in kids recommended, also 50%
who get recurrence in residual thyroid tissue die from the disease

Prognosis - age < 40 better. Worse with increasing age

- size of tumour
 - other spread beyond gland ie tracheal or laryngeal invasion, extensive pulm disease
- (?)LN involvement - not major effect on survival
- Males worse
- Aneuploidy, overexpression of p21 ras,

Follicular.
10%, later in life, may be rubbery/soft ; M:F - 1:4 ; Follicular ca:adenoma - 1:6
May appear encapsulated and to contain colloid.
Path - looks like normal thyroid tissue.
Capsular or vascular invasion distinguishes follicular ca / adenomas. Vascular invasion is ominous - 45%
5yrs
Minimally or frankly invasive - lobectomy vs total dep on grading

fs can detect up to 40% of malignancies with low risk of false +ve.

Role if completion thyroidectomy would be performed on Dx of malignancy.
Spread - via blood to bone, lung, liver. Uncommonly to LNs.
Mets often take up I131. and may appear 10-20 years after Sx.

Hurtle cell - 3% of all.

Similar to follicular, but more likely to - be multifocal
- spread to LNs
Do not take up radioiodine

Medullary.
2-5%. Solid, hard nodule, -ve on scan, from C-cells.
Sporadic 80% 30% bilateral >30yrs when Dx
Familial 20% 100% bilateral
MEN IIa MTC late ch /adol + phaeo, PTHyperplasia. Should have TT by 10, pref by5yrs
MEN Iib - MTC may be by 5yrs + phaeo, mucosal neuromas, marfanoid habitus. TT immed on ID or by
3yrs

can secrete calcitonin (+ PGI, ACTH, 5HT)

paraneoplastic syndromes - Cushings, carcinoid
50% mets (midline nodes)
poor prog indicators
clinical: - MEN IIb
- nodal + DM
- extrathyroid extension
path - small cell, pleomorphism, poor calcitonin staining, high CEA, aneuploidy

Screening in MEN2: genetic probes ret mut on Ch 10

calcitonin measures, +/- pentagastrin stimulation for FU of pts with MTC

Undifferentiated.
3%. Old women. May arise from a pap. or foll. ca Locally aggressive, rapidly enlarging.
Spread to LNs and lungs.
XRT and chemo some use, I131 no use.
Mean survival 6/12

? Total thyroidectomy.
Unnecessary if - patient would not comply with T4 Rx
- benign nodule
- occult papillary ca (< 1cm), without metastasis
- follicular ca with minimal capsular invasion
 Indicated otherwise because - recurrent cancer seen in other lobe in 7 % if left
- I131 used more easily if total has been done
- allows follow-up with thyroglobulin level
- Re-operative Sx is difficult & dangerous
Total should be done if neck has been irradiated in past because their ca is multifocal.
Main argument against total is the incidence of hypoPTism - ~10%

Post-op Mx
TSH suppression is beneficial
Should ensure that TSH is <0.1. Usually give 150-200mcg/day

Role of I131 scan

For - follow-up at 2-3/12
- Rx of secondaries - effective in (?)20% of papillary, most follicular
- ?prophylaxis - evidence increasing for its value as adjuvant Tx
Need TSH >30 & no residual Cx thyroid tissue for scan
Thus need to withdraw T4 rx for 2/52
Major SE is parotitis - self-limiting
rpt at 9-12/12

Thyroglobulin - may be a useful tumour marker in follicular & papillary

Rising level = recurrent disease

Chemo - controversial, doxorubicin 30% response + inc survival

PARATHYROID DISEASE

Embryology
Thymus from 3rd pouch, migrates medially and caudally in 6th week
Inf parathyroids also from 3rd pouch, migrates with thymus initially, separates in 8th week
Sup parathyroids from 4th pouch, in association with the lateral lobes of the thyroid
5th pouch is rudimentary -"ultimobranchial bodies" - form the C-cells of thyroid
Variants
-Cystic structure s'times at one end of a PT gland is a remnant of a pharyngeal pouch.
"Cyst of Kursteiner"
- tissue behind thyroid s'times shows groups of PT cells - "Erdheim's nests"
- multiple glands arising from a single primordium
- inf gland located in thymus

PT glands anatomy
88% have 4, 6% have fewer, 3% 3 glands (most missed) 6% have more n=5-11 (study by Gilmore,
1938).
2x3x7mm, Combined weight 120mg, superior glands smaller. Tan/Yellow/Reddish-brown.
Composed of chief (light & dark Chief cells & Waterclear cells) & oxyphil cells + fat.
Blood supply - ITa. Some collateral supply proximal to the hilum
- if inf gland is in mediastinum, blood may be from int mammary artery

Upper PT from 4th branchial pouch, usually above & behind level at which RLn crosses ITa
Most of the others are subcapsular behind upper pole of thyroid, intrathyroid uncommon
If ectopic, more dorsally displaced, so may lie b/w thyroid & oesophagus or even behind
oesophagus. Rarely found in carotid sheath.
Post to RLN, > ITA

Lower PT from 3rd branchial pouch with thymus. Significant caudal migration during development.
 Usually located within 2cm of lower pole of thyroid, most commonly on post-lat aspect of inf pole.
Next most common is below or lateral to inf pole May be multiple, may remain in thymus 25-40%
Ant to RLN, < ITA

Abnormal glands more often in abnormal positions

Sup PT may migrate to a position from upper level of thyroid down to aortic arch.
Have not been described in ant mediastinum, and remain behind RLn
Inf PT may be in either ant or post mediastinum. In thymus in 14%.
Secondary hyperPTism glands usually in normal position (?due to inflammation)

Pathophysiology
ECF calcium is 48% ionized, 46% bound - esp to albumin, 6% complexed to organic anions
If blood pH goes up (hyperventilation), more Ca becomes protein-bound get symptoms of hypocalcaemia
PTH is major regulator of ionized calcium
Effects - kidney - increases Ca resorption by PCT
- increases activation of VitD
- increases excretion of PO4 & HCO3 via cAMP mediated process
- bone - mobilizes Ca and stimulates o'clasts & o'blasts
- gut - indirect effect by activating VitD which increases absorption

Hyperparathyroidism classification
Primary - autonomous function of 1 or more PT glands
Secondary - excessive PTH production in response to chronic hypocalcaemic stimulus - usually CRF, also
VitD def / malabsorption. Pathophysiology is due to incr in plasma PO4,
secondary decr in ionized calcium, most normocalcaemic, almost all have osteodystrophy
Tertiary - autonomous PT function from long-standing secondary, usually in ESRF. Glands are
hyperplastic or adenomatous
Aet - association with neck irradiation.

Primary - F = 2x M, Peak incidence 5th decade, 90% sporadic, most due to single adenoma
- familial - MEN I and IIa. Due to mutation of the Ret oncogene - chromosome 11
- usually due to hyperplasia of 1-2 glands
- as isolated trait gen C cell hyperplasia
Overall - >80% due to single adenoma
- 10-15% due to hyperplasia
- small number due to multiple adenomas 3-4%, or carcinoma 2%

Clinically
Symptoms - Many kids are asymptomatic - some report rertrospective symptoms
Mild symptoms - poor concentration, mild depression, lassitude, fatiguability, constipation,
polydipsia & polyuria
Bone pain - vague bony aching, arthralgia (esp in secondary) 25%
Stones - renal calculi or less often nephrocalcinosis 60%
Abdominal groans - mild pain from constipation, more severe pain from PU 8%, pancreatitis 2%
Psychic moans - subtle changes to marked organic psychosis & dementia. Most acute form is
hypercalcaemic crisis

Examination - occasionally mass is palpable (mass palpable in 50% of carcinoma).

"Band keratopathy" - corneal calcification seen on slit lamp occasionally
Focal swelling of bone (brown tumours) - occasionally
ST calcification in secondary

DDx for hyperCa

- 45% Endocrine disorders - HyperPTism
- thyrotoxicosis - usually obvious, s'times difficult in elderly,
- Addisons, Phaeo
 - 45% Malignancy - primary - HHM - breast, lung, kidney, bladder
- secondary - HHM or lytic lesions
- multiple myeloma, leukaemias
- PTH-rp: 80AAs same, can measure
- 3% Granulomatous diseases - sarcoid
- TB etc
- 4% Increased intake/decreased excretion - milk-alkali - ? secondary to PU from HyperPTism
- VitD toxicity,
- drugs (thiazides, Li),
- Others- immobilization
- familial hypocalciuric hypercalcaemia - Fhx (AD), low urinary calcium, PTH normal.
Benign
- idiopathic hyperca2+ of childhood, long term TPN

Dx - high PTH - 2-site immunoradiometric for PTH is accurate, minimal cross-reactivity

- hypercalcaemia - 3 times if borderline (no torniquet, with patient off thiazides & Li) 2.58-4.82
Normocalcaemic hyperPTism in some stone formers. Upper normal Ca, high PTH
Correction for albumin - add 0.02mmol/l for each g/l below 40
- PO4 - low-normal in primary )Normal in other
- Cl high (secondary to decreased urinary resorption of HCO3), Uric acid high )causes hyperCa2+
- Cr -
- ALP - useful indicator of bone disease
- Mg - in 15% of primary hyperPTism
- Protein electrophoresis
- Urinary calcium - low in familial hypocalciuric hypercalcaemia, usually high in primary
These tests adequate in > 90%
- renal tubular absorption of phosphate, urinary cAMP sometimes useful

XR changes - densitometry to show osteopenia

- subperiosteal resorption of bone (esp middle phalanges, radial side),
loss of terminal phalangeal tufts
- bone cysts & brown tumours = osteitis fibrosa cystica - rarely seen now
- "Rugger jersey spine", "Pepper pot skull" - other descriptions of severe disease
- nephrocalcinosis, renal calculi can be seen on plain films
- CXR needed to look for sarcoid

Localization
- key to success is exploration by experienced Sx
- US - good in neck. Cant distinguish PT from LN
- Thallium-Technetium scan - good for glands outside of thyroid, 80% success. Spec dec with thyroid
disease - false + with Cx Lns, lymphoma, sarcoid
- 99Tc sestamibi scan - inc accuracy, ? Mechanism
- MRI, CT, Selective venous sampling - mainly for recurrent disease

Indications for surgery

Primary
Untreated, increased incidence of death from CV disease
Indication for Sx in asymptomatic patients is difficult - some argue that almost all need Sx, esp
1. Persistent calcium > 2.9mmol/l
2. Osteopenia (densitometry), or ALP > 350
3. Renal calculi or nephrocalcinosis on AXR
4. Cr clearance down 30%
5. Patient < 50 in whom long term follow-up impractical

All symptoms become better after parathyroidectomy

 Secondary
Can usually be controlled non-operatively
In CRF - VitD, high calcium intake, low dietary phosphate, Al hydroxide to bind PO4 all useful
In dialysis - can add calcium to dialysate after lowering phosphate level.
Sx if - intractable bone pain, pruritus, soft tissue deposition despite cons Mx (often = tertiary)

Tertiary - generally need Sx - total PTectomy + autotransplant

Parathyroidectomy
Preparation
Large volumes of IV fluid +/- frusemide in severe hypercalcaemia with vomiting & polyuria
May occasionally need dialysis
Preop calcitriol in those with high ALP & secondary PTism (risk of hungry bones & profound
hypoca)
Risk of thromboembolism (heparin), risk of DU (?antacids)
Me blue 5mg/kg in 100ml NS over 1 hour prior to Sx - ddx LN, nodular thyroid

Technique
Key points.
1.Haemostasis crucial
2.Should find 4 glands. >4 found in 5%. <4 in 1.5%. Glands usually symmetrical in position
3.Sup gland usually behind RLn & above ITa. Inf gland usually below artery, in front of n.
4.Missing gland may be related to thymus, 5th gland may aslo be in thymus
5.Autotransplantation is effective.

Incision as for thyroid operation, through skin and platysma.

Mobilize both lobes of the thyroid, ligating middle thyroid vein. Gland mobilized and rolled
forward. +/- Division of fascia binding gland to trachea post-medially
Search for sup gland in normal position, in sup thyroid pedicle, within gland, retro -oesophageally,
along carotid sheath
Inf gland usually within 2cm, of lower pole of thyroid Search for Inf gland in normal position,
If not found, examine thyrothymic ligament, lower pole fat, thymic horns, +/- transCx thymectomy
If not found, examine tracheo-oesophageal groove, then behind oesophagus
If not found, ?hemithyroidectomy, open carotid sheath
Would not open chest on 1st operation
Ensure haemostasis
2-0 CCG closure +/- drain.

May be hard to difft fat from PT tissue - fat floats, gland sinks

Strategy for dealing with glands

Primary
If single adenoma found, totally removed, taking care not to breach capsule
FS to confirm identity
Exploration of other glands, identifying all four
If other enlarged glands, biopsy ? second adenoma (2%) or 2-4 gland hyperplasia (10-15%)
If all 4 are enlarged, 3.5 gland resection (leave 2 halves, wait & inspect, then remove less viable)

Secondary
Identify all glands, remove 4 or 3.5. Argue for either: no diff Vit D, Ca2= reqt & wont take vs
gland devascualrized & recurrent disease more of a problem
Autotransplant 15 x 1mm cubes into a muscle - SCM or brachioradialis, mark pockets with staple
and nonabs suture.

Carcinoma
 Suspect if Ca > 3.5, palpable neck mass, gland at operation firmer than normal, grey in colour or
adherent to surrounding tissues
En bloc resection of tumour and surrounding tissues (often requires hemithyroidectomy) and
unilateral LN dissection

Severe hypercalcaemia
"Hypercalcaemic crisis" - v. high calcium > 4 mmol/l, obtunded, low muscle tone, hyporeflexia
Cardiac arrhythmias, esp if on digoxin
Resp failure
N&V, pancreatitis, peptic ulcer
Mx :-
1. Resuscitate - hydrate with Nsaline, correct hypoNa and hypoK
- Frusemide will increase Ca excretion in a rehydrated patient. There is some
controversy, as it will contribute to ATN if patient is not rehydrated
- Mithramycin, Calcitonin will work in most in short term (2/7)
- EDTA is rarely used, due to SEs
- PO4 has been associated with cardiac arrest, therefore not used.
- Glucocorticoids - in VitD intoxication and sarcoidosis very effective
some use in cancer
rarely useful in hyperPTism
2. Make Dx - many of these patients already have a Dx of hyperPTism
3. If hyperPTism - early Sx

Complications of Sx - persistent hypercalcaemia

- permanent hypoPTism
- RLn palsy etc - less chance than after thyroidectomy

Calcium homeostasis after parathyroidectomy - most primary HPT do not need calcium supplements
Serum calcium falls after 4-12 hours, nadir at 48-72hrs. Give orally, if < 2 may need IV
Urinary calcium initially rises, then falls to undetectable
Functional hypoparathyroidism for up to 3 weeks
Postop metabolic acidosis & hypomagnasemia
Hypomagnasemia can contribute to functional hypoPTism as Mg is needed for normal PTH release
& some Mg is deposited in bones in the"hungry bones" syndrome

Hypocalcaemia more common if - Sx is for secondary (~all need Ca)

- ALP is high or bone pain is prominent
- both sides of the neck are explored
- large adenoma
- second operation

Strategy after failed Cx exploration - 5-15% failure rate 2-3% exp Sx

Review original Dx - familial hypocalciuric hypercalcaemia in 10% of those with "failure"
Check operative note, if 4 found, 5th is likely to be mediastinal
If not, may need to reexplore neck - 90% success
Localization studies needed

Of subsequently recovered PTs, 80% are in neck, 20% in mediastinum

Failure rate for mediastinal exploration - 35%
High re-op morbidity - RLN palsy 8% temp, 4% perm, hypoPTism 13%

HyperPTH in pregnancy
mild asymptomatic - monitor M, oral biphosphonates
- monitor F post delivery for tetany, hypoglycaemia
marked inc Ca2= - Sx in T2
MULTIPLE ENDOCRINE NEOPLASIA
MEN-1 (Wermer Sy)
Long arm of Chr 11
Pancreatic, pituitary & parathyroid lesions
key feature is multiplicity

Primary hyperparathyroidism
- commonest & often the only manifestation
- calcium may be only marginally elevated, and PTH may be marginal
- hyperplasia is typical pathology, and espacially in teenagers, the glands may not be very big
- Sx - total PTectomy & autotransplant/cryopreservation, + thymectomy (5th gland & risk of thymoma)

Pancreatic adenomas
- non-functional lesions most common - "incidentalomas". ?Should remove if >2cm or enlarging >1.6
- PPomas > gastrinomas > insulinomas
- gastrinomas - pw PU symptoms or diarrhoea
- dyspepsia with high gastrin & calcium is 2nd most common presentation of MEN1
Parathyroidectomy often cures the PU, & malignancy should be considered if gastrin stays high or a
lesion is seen in HoP. Gastrinomas in MEN1 are more often in duodenum - often microadenomas,
which sometimes involve LNs but rarely spread to liver
- insulinomas - most common sporadic islet cell tumour, but only seen in 5% of MEN1patients
Can be presenting feature, often in children with poor school performance

Pituitary tumours
- prolactinomas mainly, others possible

Others
- adrenal - esp incidentalomas (can be bilateral & this should raise possibility of MEN1)
- atypical malignant carcinoid of thymus or bronchus - DDx difficult, often misDx if FHx unknown
- gastroduodenal lesions - mucosal carcinoids & neuro-endocrine hyperplasia

MEN-2a (Sipple Sy) - Ret oncogene (also involved in Men-2b & Familial MTC)
Phaeochromocytoma - often bilateral, occasionally extra-adrenal, usually benign
- 7% of patients with phaeo also have MTC

Medullary carcinoma of the thyroid (MTC) - can be familial wthout other markers of MEN2a
- aapears 1st, PTH and phaeos years later
- C cell hyperplasia may precede MTC by many years
- MTC is multifocal, therefore need total thyroidectomy
- calcitonin is used for screening. If borderline, can do pentagastrin stimulation

Hyperparathyroidism - in 50% of cases

- often due to hyperplasia

MEN-2b
MTC - tend to be more malignant than in MEN2a
Phaeochromocytoma
Need more agressive Sx than IIa

Dysmorphic features - neuromas on buccal mucosa, tongue, labia, conjunctivae, larynx, GIT
- enlarged corneal nerves
- blubbery lips
- soft-tissue prognathism
- habitus resembling Marfan's
- cafe-au-lait spots, cutaneous neurofibromas