Parathyroid Class for Anaesthesia Team

1. DISORDERS OF THE
PARATHYROID
GLANDS & ITS
MANAGEMENT

2. SELF ASSESSMENT QUESTIONS
1. Regarding parathyroid glands
a. The chief cells secrete parathyroid hormone
b. They develop from the third and fourth pharyngeal pouches
c. The normal plasma level of intact parathyroid hormone is 10-55pg/mL
d. The most common abnormality is multiple gland hyperplasia
e. Hyperparathyroidism is associated with both MEN type I and II
2. With regards to calcium metabolism
a. It is the ionised calcium concentration which influences the physiological effects
b. The normal value of ionised calcium is 2.12-2.65mmol/l
c. Calcitonin plays a major role in calcium homeostasis in humans
d. Absorption of Ca2+ from the GI tract is regulated by parathyroid hormone
e. 98-99% of filtered calcium is reabsorbed in the kidney
3. Regarding hyperparathyroidism
a. The most common cause of primary hyperparathyroidism is a solitary adenoma
b. The majority of patients with hyperparathyroidism are symptomatic at diagnosis
c. The incidence of primary hyperparathyroidism in the UK is thought to be 25 per 100,000
d. The commonest cause of secondary hyperparathyroidism is chronic renal failure
e. Technetium -99 m sestamibi scanning is the most accurate method for the preoperative
localization of the parathyroid glands

3. 4. Regarding anaesthesia for parathyroid surgery
a. An acceptable preoperative calcium level is <3mmol/l
b. The usual indication for surgery is primary hyperparathyroidism from a
parathyroid adenoma
c. The intraoperative use of methylene blue can cause a false low SpO2
reading.
d. Minimally invasive parathyroidectomy can be done under superficial
cervical plexus block and sedation
e. From an airway obstruction point of view a partial lesion of the recurrent
laryngeal nerve is more serious than a complete lesion
5. With regard to the perioperative management of hyperparathyroidism
a. Intravenous Bisphosphonate is the first line drug therapy in the treatment
of life threatening hypercalcaemia
b. Serum calcium should be checked at 6 and 24 hrs after parathyroidectomy
c. Postoperative hypocalcaemia and hypomagnesaemia from “hungry bones”
is seen more often after surgery for secondary hyperparathyroidism.
d. Positive Chvostek’s sign refers to carpopedal spasm elicited by cuff
inflation.
e. Airway encroachment is common with parathyroid tumours

4. Endocrine surgeries have been on the rise for the last few
years. During surgery, endocrine disorders present unique
challenges to the endocrinologist and to the attending
anesthesiologist. The endocrine, electrolyte and metabolic
disturbances resulting from such disorders can have a
profound effect on the normal human physiological milieu.
Surgery of parathyroid glands is no exception and is associated
with a multiple challenges during pre-, intra-, and post-
operative period. Pre-op examination and optimization is
essential so as to prevent any intra-op or post-op
complications. The most striking electrolyte disturbance
during parathyroid surgery is the imbalance of calcium levels
in the body and the main emphasis during the entire peri-
operative period revolves around the maintenance of normal
serum calcium levels.
INTRODUCTION

5. Disorders of the Parathyroid
Glands
Maintenance of calcium, phosphate and
magnesium homeostasis is under the
influence of two polypeptide hormones;
parathyroid hormone(PTH), and calcitonin
(CT), as well as a sterol hormone,
1,25 dihydro-cholecalciferol (1,25 (OH)2D3

6. Disorders of the Parathyroid
Glands
These hormones regulate the flow of
minerals in and out of the extracellular
fluid compartments through their actions
on intestine, kidneys, and bones.

7. Disorders of the Parathyroid
Glands
The PTH acts directly on the bones and
kidneys and indirectly on the intestine
through its effect on the synthesis of 1,25
(OH)2D3.
Its production is regulated by the
concentration of serum ionized calcium.
Lowering of the serum calcium levels
will induce an increased rate of
parathyroid hormone secretion

8. Disorders of the Parathyroid
Glands
Calcitonin is released by the “C” cells
(parafollicular cells in the thyroid gland)
in response to small increases in plasma
ionic calcium.
It acts on the kidney and bones to restore
the level of calcium to just below a normal
set point which in turn inhibits secretion of
the hormone.

9. Disorders of the Parathyroid
Glands
Calcitonin is therefore the physiological
antagonist of PTH. The two hormones act
in concert to maintain normal
concentration of calcium ion in the
extracellular fluid.

11. Disorders of the Parathyroid Function
Hyperparathyroidism
Primary hyperparathyroidism is due to
excessive production of PTH by one or
more of hyper functioning parathyroid
glands.
This leads to hypercalcemia which fails to
inhibit the gland activity in the normal
manner.

12. Disorders of the Parathyroid Function
Hyperparathyroidism
The cause of primary hyperparathyroidism
is unknown.
A genetic factor may be involved.
The clonal origin of most parathyroid
adenomas suggests a defect at the level
of the gene controlling the regulation
and/or expression of parathyroid hormone.

13. Disorders of the Parathyroid Function
Hyperparathyroidism
The incidence of the disease increases
dramatically after the age of 50 and it is 2-4 folds
more common in women.
A single adenoma occurs in about 80% of
patients with primary hyperparathyroidism.
Four glands hyperplasia account for 15-20% of
cases.
A parathyroid carcinoma could be the etiology in
a rare incidence of less then 1%.

14. Disorders of the Parathyroid Function
Clinical Features:
The two major sites of potential complications
are the bones and the kidneys.
The kidneys may have renal stones
(nephrolithiasis) or diffuse deposition of calcium-
phosphate complexes in the parachyma
(nephrocalcinosis).
Now a days such complications are seen less
commonly and around 20% of patients or less
show such complications.

15. Disorders of the Parathyroid Function
Clinical Features:
In skeleton a condition called osteitis fibrosa
cystica could occur with sub-periosteal
resorption of the distal phalanges, distal
tappering of the clavicles, a “salt and pepper”
appearance of the skull as well as bone cysts
and brown tumors of the long bones.
Such overt bone disease even though typical of
primary hyperparathyroidism is very rarely
encountered.

16. Disorders of the Parathyroid Function
Clinical Features:
Now a days almost 90% of diagnosed
cases in the developed countries are
picked up by routine screening for calcium
level using the new automated machines.

17. Disorders of the Parathyroid Function
Clinical Features:
Other symptoms include muscle
weakness, easy fatigability, peptic ulcer
disease, pancreatitis, hypertension, gout
and pseudogout as well as anemia and
depression have been associated with
primary hyperparathyroidism.

19. 1. Primary
hyperparathyroidism
A. Solitary adenomas
B. Multiple endocrine
neoplasia
2. Lithium therapy
3. Familial
hypocalciuric
hypercalcemia
1. Vitamin D
intoxication
2. 1,25(OH)2D;
sarcoidosis and
other granulomatous
diseases
3. Idiopathic
hypercalcemia of
infancy
Differential Diagnosis
Causes of Hyper-calcemia
Parathyroid - related Vitamin D – related

20. Differential Diagnosis
Causes of Hypercalcemia
Malignancy - related
1. Solid tumor with
metastases(breast)
2. Solid tumor with
humoral mediation of
hypercalcemia (lung
kidney)
3. Hematologic
malignancies (multiple
myeloma, lymphoma,
leukemia)
Associated with high
bone turnover
1. Hyperthyroidism
2. Immobilization
3. Thiazides
4. Vitamin A intoxication
Assocated with Renal
Failure:
1. Severe secondary
hyperparathyroidism
2. Aluminum intoxication
3. Milk alkali syndrome

21. Diagnosis
The presence of established
hypercalcaemia in more than one serum
measurement accompanied by elevated
immunoreactive PTH is characteristic
(iPTH)

22. Diagnosis
Serum phosphate is usually low but may be
normal.
Hypercalcemia is common and blood
alkaline phosphatase (of bone origin) is
raised.

23. Other Diagnostic tests
Radiograph:
Plain X-ray of hands can be diagnostic
showing sub periosteal bone resorption
usually on the radial surface of the distal
phalanx with distal phalangeal tufting as
well as cysts formation and generalized
osteopenia.

24. Other Diagnostic tests
Pre-operative localization of the abnormal
parathyroid gland(s):
• Ultrasonography
• MRI
• CT
• Thallium 201 – Tehcnichum99m scan
(subtraction study)

25. Parathyroid Scan
Dual phase MIBI Scan Tc-Tl Subtraction Scan

26. Treatment
A large proportion of patients have
“biochemical” hyperparathyroidism but
with prolonged follow up they progress to
overt clinical presentation.
Resection of the parathyroid lesion is
curative with recurrences observed mainly
in the multiple glandular disease.

27. Medical Treatment of the
hypercalcaemia
In acute severe forms the main stay of
therapy is adequate hydration with saline
and forced diuresis by diuretics to increase
the urinary excretion of calcium rapidly
along with sodium and prevent its
reabsorption by the renal tubules.

28. Other agents
• Glucocostiroids
– In hypercalcaemia associated the
hematological malignant neoplasms
• Mythramycin
– A toxic antibiotics which inhibit bone
resorption and is used in hematological and
solid neoplasms causing hypercalcaemia.

29. Other agents
• Calcitonin
– Also inhibit osteoclast activity and prevent
bone resorption
• Bisphosphonates
– They are given intravenously or orally to
prevent bone resorption.

30. Other agents
• Phosphate
– Oral phosphate can be used as an
antihypercalcaemic agent and is commonly
used as a temporary measure during
diagnostic workup.
• Estrogen
– It also decrease bone resorption and can be
given to postmenopausal women with primary
hyperparathyroidism using medical therapy

31. Surgery
Surgical treatment should be considered
in all cases with established diagnosis of
primary hyperparathyroidism.
During surgery the surgeon identifies all four
parathyroid glands (using biopsy if
necessary) followed by the removal of
enlarged parathyroid or 3 ½ glands in
multiple glandular disease.

32. Secondary hyperparathyroidism
An increase in PTH secretion which is
adaptive and unrelated to intrinsic disease
of the parathyroid glands is called
secondary hyperparathyroidism.
This is due to chronic stimulation of the
parathyroid glands by a chronic decrease
in the ionic calcium level in the blood

34. Major causes of chronic hypocalcemia other
than hypoparathyroidism
• Deficiency of vitamin D or calcium
• Decreased intestinal absorption of vitamin
D or calcium due to primary small bowel
disease, short bowel syndrome, and post-
gastrectomy syndrome.
• Drugs that cause rickets or osteomalacia
such as phenytoin, phenobarbital,
cholestyramine, and laxative.

35. Major causes of chronic hypocalcemia other
than parathyroprival hypoparathyroidism
• States of tissue resistance to vitamin D
• Excessive intake of inorganic phosphate
compunds
• Psudohypoparathyroidism
• Severe hypomagnesemia
• Chronic renal failure

36. Hypoparathyroidism
Deficient secretion of PTH which
manifests itself biochemically by
hypocalcaemia, hyperphosphatemia
diminished or absent circulating iPTH and
clinically the symptoms of neuromuscular
hyperactivity.

37. Hypoparathyroidism
Causes:
•Surgical hypoparathyroidism
The commonest
After anterior neck exploration for
thyroidectomy, abnormal parathyroid gland
removal, excision of a neck lesion.
It could be due to the removal of the
parathyroid glands or due to interruption of
blood supply to the glands.

38. Hypoparathyroidism
Causes:
• Idiopathic hypoparathyroidism
– A form occurring at an early age (genetic
origin) with autosomal recessive mode of
transmission “multiple endocrine deficiency –
autoimmune-candidiasis (MEDAC) syndrome”
– “Juvenile familial endocrinopathy”
– “Hypoparathyroidism – Addison's disease –
mucocutaneous candidiasis (HAM) syndrome”

39. Hypoparathyroidism
Causes:
• Idiopathic hypoparathyroidism
– Circulating antibodies for the parathyroid
glands and the adrenals are frequently
present.
– Other associated disease:
• Pernicious anemia
• Ovarian failure
• Autoimmune thyroiditis
• Diabetes mellitus

40. Hypoparathyroidism
Causes:
• Idiopathic hypoparathyroidism
– The late onset form occurs sporadically
without circulating glandular autoantibodies.
• Functional hypoparathyroidism
– In patients who has chronic
hypomagnesaemia of various causes.
– Magnesium is necessary for the PTH release
from the glands and also for the peripheral
action of the PTH.

41. A. Neuromuscular
– The rate of decrease in serum calcium is
the major determinant for the development
of neuromuscular complications.
– When nerves are exposed to low levels of
calcium they show abnormal neuronal
function which may include decrease
threshold of excitation, repetitive response
to a single stimulus and rarely continuous
activity.
Hypoparathyroidism
Clinical Features:

42. A. Neuromuscular
– Paresthesia
– Tetany
– Hyperventilation
– Adrenergic symptoms
– Convulsion (More common in young people and it
can take the form of either generalized tetany
followed by prolonged tonic spasms or the typical
epileptiform seizures.
– Signs of latent tetany
• Chevostek sign
• Trousseau sign
• Extrapyramidal signs (due to basal ganglia calcification)
Hypoparathyroidism
Clinical Features:

43. B. Other clinical manifestation
1. Posterio -lenticular cataract
2. Cardiac manifestation:
– Prolonged QT interval in the ECG
– Resistance to digitalis
– Hypotension
– Refractory heart failure with cardiomegally
can occur
Hypoparathyroidism
Clinical Features:

44. B. Other clinical manifestation
3. Dental Manifestation
Abnormal enamel formation with delayed or
absent dental eruption and defective dental
root formation.
4. Malabsorption syndrome
Presumably secondary to decreased
calcium level and may lead to steatorrhoea
with long standing untreated disease.
Hypoparathyroidism
Clinical Features:

45. Hypoparathyroidism
Diagnosis:
In the absence of renal failure the
presence of hypocalcaemia with
hyperphosphatemia is virtually diagnostic
of hypoparathyroidism.
Undetectable serum iPTH confirms the
diagnosis or it can be detectable if the
assay is very sensitive.

46. Hypoparathyroidism
Treatment:
The mainstay of treatment is a
combination of oral calcium with
pharmacological doses of vitamin D or its
potent analogues.
Phosphate restriction in diet may also be
useful with or without aluminum
hydroxide gel to lower serum phosphate
level.

47. Emergency Treatment for Hypocalcaemic
Tetany:
Calcium should be given parenterally till
adequate serum calcium level is
obtained and then vitamin D
supplementation with oral calcium should
be initiated.

48. Pseudohypoparathysoidism and
Pseudopseudohypoparathyroidism
A rare familial disorders with target tissue
resistance to PTH.
There is hypocalcaemia,
hyperphosphataemia, with increased
parathyroid gland function.
There is also a variety of congenital
defects in the growth and development of
skeleton including:
• Short statue
• Short metacarpal and metatarsal bones

50. • Endocrine surgeries and emergencies pose unique challenges to
the attending anaesthesiologists and the intensivists.
• The most striking electrolyte disturbance during parathyroid
surgery is the imbalance of calcium levels in the body and the
main emphasis during the entire peri-operative period revolves
around the maintenance of normal serum calcium levels.
• The precautionary measures have to be taken during
administration of anesthesia as thiopentone and volatile
anaesthetic prolong the QTc interval. Similarly few drugs like
macrolides, quinolones, antifungals like ketoconazole and
fluconazole should better be avoided during the peri-operative
period as they also have a potential to prolong QTc interval.
• Renal scans and ultrasound are sometimes carried out for
diagnosis of renal stones which is very useful for the formulation
and planning for peri-operative renal protection strategies when

51. Pre-op Optimization
The clinical symptomatology is diverse and may
include moderate to severe dehydration,
tachycardia, polyuria, anorexia, vomiting, extreme
weakness lethargy, and mental signs and
symptoms including psychosis which needs
thorough investigations. In untreated cases the
condition can deteriorate rapidly and can
progress to coma and collapse.

52. The emergency therapeutic interventions for optimization of
hypercalcaemia include:
• Infusion of normal saline@ 2.5-3.0 ml/kg/hr with a maximum
optimization up to 4-6 liters.
• Biphosphonates such as Pamidronate 60 mg is the first line of
drug for treatment of life threatening hypercalcaemia (Ca2+>4.5
mmol/l)
• Infusion of phosphate - to lower life threatening hypercalcaemia
(>4.5 mmol/l)
• Calcitonin in doses of 3-4 U/kg - either intravenously (IV) or
subcutaneously to lower the calcium levels.
• Plicamycin and mithramycin administration is done cautiously as
these drugs have a very narrow therapeutic index.
• Frusemide is administered for forced saline diuresis as it inhibits
tubular reabsorption of calcium while simultaneously measuring
central venous pressure.
• Although controversial, corticosteroids administered during the
acute phase possibly inhibit further absorption of calcium from the

53. Regional
vs.
General
Anaesthesia

54. Premedication
• Alprazolam
• H2 antagonist ranitidine
• Sodium citrate
• Glycopyrrolate 0.2 mg
Airway management
pathological fractures due to prolonged
hypercalcemia?
unstable cervical spine as a result of lytic
lesions

55. Hypercalcaemia may cause inadequate
reversal due to unpredictable augmentation of
non-depolarizing neuromuscular blockade,
thus possibly leading to post-operative
hypoxemia and respiratory obstruction.
Extubation should be carried out in a fully
awake state and after establishing a regular
breathing pattern with adequate tidal volume
and muscle strength.

56. POST-OP COMPLICATIONS
• Bleeding: Post-operative episode of bleeding and subsequent
development of hematoma can cause respiratory obstruction.
Therefore, all the dressings should be checked thoroughly before
the patient is shifted to their respective wards from the recovery
area.
• Metabolic abnormalities: Hypophosphatemia, hypomagnesemia,
and hypokalemia can prove catastrophic during post-op period and
should be rectified at the earliest. The combined picture projects a
constellation of clinical symptomatology such as cardiac failure,
dysarrhythmias, neuromuscular irritability hemolysis, platelet
dysfunction, and leucocyte dysfunction.
• Hypocalcemic tetany: It occurs due to drastic reduction in post-
operative serum calcium levels four to five days post-operatively
and is clinically manifested by laryngeal spasms, seizures, and
presence of Chvostek's and Trousseau's sign.

57. Minimally invasive parathyroidectomy
 Minimally invasive radio-guided
parathyroidectomy is being performed with
a gamma probe in cases of persistent and
recurrent hyperparathyroidism.
 The endoscopic dissection with
insufflations of gas has also been
performed for minimally invasive
endoscopic parathyroidectomy. The
bilateral neck exploration is an added
advantage

58. • Recurrent laryngeal nerve (RLN) injury: Unilateral RLN nerve injury is
mostly asymptomatic as there occurs compensatory over adduction of the
uninvolved cord and is typically characterized by the development of
hoarseness of voice. Unopposed adduction of the cord can occur during
bilateral RLN injury and leads to closure of glottis. Endotracheal intubation
is a temporary relief measure and tracheostomy is a definite long term
preventive measure.
• Soft tissue trauma and edema: It can progress to bullous glottic edema
involving the glottis and the pharynx. The onset and origin of this
complication remains controversial with no definite preventive measures.
• Respiratory obstruction: Respiratory obstruction can occur due to enlarging
hematoma from the wound site bleeding, bilateral recurrent laryngeal
nerve injury, bullous glottis edema and metabolic abnormalities.[31,32]
• Renal complications: The chances of renal dysfunction are high in patients
who already have some renal disease associated with hypercalcemia pre-
operatively.
• Post-op pain: Numerous techniques and drugs are available nowadays to
alleviate even a high intensity pain. Pre-emptive analgesia and patient
controlled analgesia are the new dimensions in the pain relief category
which are getting very popular at present.