discussion on parathyroid

1. DISCUSSION ON THE
PARATHYROID’S – NORMAL
AND ABNORMAL
Dr. Mausamin Hathidara

2. EMBRYOLOGY
 The third branchial pouch gives rise to the
inferior parathyroid glands in close association
with the primordia of the the thymus gland. As
the thymus descends to the anterior
mediastinum, parathyroids III follow along,
ultimately coming into contact with the
developing thyroid caudal to parathyroids IV.
 The parathyroid glands derived from pouch IV
take a more direct route to come in contact
with the thyroid, and become the more
cephalad or superior glands.
 A portion of pouch IV contributes a lateral C-
cell component to the thyroid.
 The parathyroids usually (~80%) lie near the
posterolateral capsule of the thyroid lobes.

3. ANATOMY
 The superior parathyroid glands are most commonly found about the
middle third of the thyroid lobe, at the level of the cricothyroid
junction, and near the point where the recurrent laryngeal nerve
passes beneath the inferior pharyngeal constrictor to enter the
larynx
 The inferior glands are usually found near the lower pole of the
thyroid lobe or below the lobe in the thyro-thymic ligament. They
commonly lie below the inferior thyroid artery and anterior to the
recurrent laryngeal nerve

4. ANATOMY(contd.)

5. ANATOMY(contd.)

6. PHYSIOLOGY
 Parthyroid Hormone (PTH)
 Secreted by the Chief cells
 Levels are inversely conrolled by [Ca2+ ]
 Effects:
 Tubular reabsorption of Ca2+
 Osteoclastic resorption of bone
 Intestinal absorption of Ca2+
 Synthesis of 1-25DHCC (active Vit. D)
 Excretion of phosphate

7. PATHOLOGY
 HYPERPARATHYROIDISM
 1 : 1,000 prevalence
 F : M 2 : 1
 Usually mild / asymptomatic

8. ETIOLOGY
 Primary (increased PTH, normal or raised Ca 2+ )
 Adenoma 90%
 Hyperplasia 10%
 Carcinoma < 1%
 Secondary ( increased PTH appropriate to low Ca 2+ )
 Chronic Renal Failure
 Vitamin D Deficiency
 Tertiary
 Continued excess PTH secretion following prolonged secondary
hyperparathyroidism

9. PRESENTATION
 Classic Pentad : Kidney stones, Painful bones, Abdominal groans,
Psychic moans, Fatigue overtones
Bones Bone pain, fractures, arthralgia
Renal Stones, polyuria
G.I. Pain, duodenal ulcer, pancreatitis
Neuro. Depression, apathy
Cardiac Hypertension, heart block

10. PRESENTATION ( contd.)
Symptom %
Asymptomatic hypercalcaemia 50
Renal stones 28
Arthralgia 5
Peptic Ulcer 4
Hypertension 4
Bone disease / MEN 1 / others 9

11. DIAGNOSIS
 S. Calcium : increased (except in normocalcemic variant)
 S. iPTH : inappropriately high
 S. Phosphate : Decreased or low normal
 S. Chloride : increased or high normal
 S. Magnesium : unchanged or decreased (OFC)
 Alkaline Phosphatase : normal or increased
 Calcitriol : normal or increased
DIAGNOSIS IS BIOCHEMICAL AND LOCALISATION NOT REQUIRED FOR
DIAGNOSIS

12. HYPERCALCEMIA (D.D.)
 Hyperparathyroidism
 Malignancy – Hematological (MM), Solid tumors (PTHrP)
 Endocrine – Hyperthyroidism, Addisonian crisis, VIPoma
 Granulamatous diseases – Tb, Sarcoidosis, Histoplasmosis
 Drugs – Thiazides, Lithium, Vitamin A/D intoxication
 Miscellaneous – Pagets, BFHH, Immobilisation, Milk-Alkali syndrome

13. MANAGEMENT
PARATHYROIDECTOMY WHEN -
 Symptomatic hyperparathyroidism
 Serum Calcium : > 12 mg/ dl (>1 mg/ dl UL)
 Reduced creatinine clearance by 30 %
 Medical Surveillance is either undesirable or impossible
 Hypercalciuria ( > 400mg /day )
 Reduced cortical bone density (< -2.5 T score BMD)
 Young patient ( < 50 )
*NATIONAL INSTITUTE OF HEALTH – 2002 CONSESUS.

14. LOCALISATION
STUDY ADVANTAGES DISADVANTAGES
PRE-OPERATIVE - NONINVASIVE
Sestimibi scan Planar and 3D SPECT False positive’s
Ultrasound Juxta/intrathyroid, cheap False positives’s
CT Ectopics, recurrence Cost, Radiation
MRI Ectopics, recurrence Cost
PRE-OPERATIVE - INVASIVE
FNA Biopsy LN / Parathyroid Experience
Angiogram Roadmap to sample, Embolise Experience
Venous sampling Equivocal cases Experince, cost
INTRAOPERATIVE
PTH assay Confirm removal cost

15. TREATMENT OPTIONS
 Bilateral neck exploration (Traditional)
 Minimally Invasive Parathyroidectomy (MIP)
 Video-Assisted Parathyroidectomy (VAP)
 Endoscopic Parathyroidectomy (EP)
 Medical Management
 Wait and watch

16. TRADITIONAL
PARATHYROIDECTOMY
 Bilateral neck exploration under general anesthesia with/without frozen
section confirmation.
 Admission for 2-5 days
 Complication rates 1-3% (General - bleeding and wound complications
such as seromas and infection; Specific - transient and permanent
vocal cord palsy and hypoparathyroidism)
 Cure rate (normocalcemia 6 months postoperatively) of > 95%
 Excellent results and still in vogue

17. MINIMALLY INVASIVE
PARATHYROIDECTOMY
 First advocated by Roth in 1975
 Preoperative localisation essential
 Done under regional or local anesthesia
 Intraoperative staining with sudan black or oil red – O to confirm,
now replaced with rapid PTH assay
 Unilateral Parathyroidectomy introduced by Tibblin in 1982 (normal
and affected gland on one side excised)

18. MINIMALLY INVASIVE
PARATHYROIDECTOMY(contd.)
PTH / Calcium
Sestemibi scan
Solitary adenoma
Unilateral exploration
>50% iPTH
Negative or MGD
Bilateral Exploration
< 50% iPTH

19. VIDEO-ASSISTED
PARATHYROIDECTOMY
 Introduced and pioneered by Paolo Miccoli
 It does not require steady gas flow, but rather a brief insufflation of
carbon dioxide to establish the operative space, which is then
maintained by external retraction
 Preoperative localization is essential and general anesthesia is
typically used, although local anesthesia might be feasible
 The rapid PTH assay was used as an adjunct
 Conversion to open parathyroidectomy occurred in 11% of patients
 The operating time was 55 minutes on average, with a median
hospital stay of 1.5 days

20. ENDOSCOPIC
PARATHYROIDECTOMY
 The first endoscopic removal of a parathyroid in the neck was reported by
Gagner in 1996
 It is generally reserved for patients with single-gland disease and requires
preoperative imaging to localize the culprit parathyroid adenoma and
guide the operation
 Generally, access for the endoscope is obtained at the manubrium, and
two additional ports are inserted laterally in the neck, anterior to the
sternocleidomastoid muscle and ipsilateral to the parathyroid tumor
 Variations on this technique exist
 Regardless of the technique used, there is a significant learning curve
associated with endoscopic parathyroidectomy

21. MEDICAL MANAGEMENT
 There are no long-term medical therapies for which data are
convincing regarding either their efficacy or safety in the treatment
of primary HPT
 Bisphosphonates such as etidronate, alendronate, and pamidronate
have been used in the treatment of Paget's disease, osteoporosis,
and hypercalcemia of malignancy
 SERM’s (raloxifene and tamoxifen ) do not reduce PTH concentrations
in patients with primary HPT. In addition, unopposed estrogen
increases the risk for endometrial hyperplasia and carcinoma, as well
as the risk for venous thromboembolism.
 Calcimimetics have demonstrated a dose-dependent reduction in PTH
and blood calcium, with larger doses causing more sustained effects.
The long-term role of calcimimetic agents such as cinacalcet has yet
to be determined for the treatment of primary HPT, but it has rapidly
become established as a mainstay in the management of secondary
HPT

22. WAIT AND WATCH ?
 It is current philosophy that the diagnosis of primary
hyperparathyroidism is, in fact, an indication for operation therapy
unless undue risk factors that can prohibit general anesthesia are
present.
 There are several reasons for this seemingly dogmatic position
There is currently no effective long-term medical therapy for primary
hyperparathyroidism.

23. WAIT AND WATCH ?(contd.)
Truly asymptomatic primary hyperparathyroidism probably does not
exist. -there is evidence that even mild hypercalcemia can influence
mentation, mood, and muscle strength profoundly in a significant
percentage of patients, particularly in the elderly population
Operative intervention by an experienced endocrine surgeon results
in a cure rate of more than 95 % with minimal morbidity and
mortality

24. SPECIAL CONDITIONS
PARATHYROID CARCINOMA :
It may be suspected preoperatively by the presence of severe symptoms,
serum calcium levels greater than 14 mg/dL, significantly elevated
PTH levels (five times normal), and a palpable parathyroid gland
Approximately 15% of patients have lymph node metastases and 33%
have distant metastases at presentation
Large, gray-white to gray-brown parathyroid tumor that is adherent to or
invasive into surrounding tissues
Treatment of parathyroid cancer consists of bilateral neck exploration,
with en bloc excision of the tumor and the ipsilateral thyroid lobe.
Modified radical neck dissection is recommended in the presence of
lymph node metastases. Prophylactic neck dissection is not advised

25. SPECIAL CONDITIONS(contd.)
FAMILIAL HYPERPARATHYROIDISM :
Isolated familial hyperparathyroidism (non-MEN), or familial
hyperparathyroidism with jaw tumors
Higher incidence of multiglandular disease, supernumerary glands, and
recurrent or persistent disease
Warrant a more aggressive approach and are not candidates for various
focused surgical approaches

26. SPECIAL CONDITIONS(contd.)
A standard bilateral neck exploration is performed, along with a bilateral
cervical thymectomy, regardless of the results of localization studies.
Both subtotal parathyroidectomy and total parathyroidectomy with
autotransplantation are appropriate
MEN1: hypercalcemia should be treated prior to treatment of gastrinoma,
because gastrin levels often decline in these patients following
parathyroidectomy
MEN2A: require total thyroidectomy and central neck dissection for
prevention/treatment of MTC, a procedure that places the parathyroids at
risk. HPT is less aggressive in these patients - only abnormal parathyroid
glands need to be resected at neck exploration. The other normal
parathyroid glands should be marked with a clip

27. SPECIAL CONDITIONS(contd.)
NEONATAL HYPERPARATHYROIDISM
Infants with neonatal HPT present with severe hypercalcemia, lethargy,
hypotonia, and mental retardation
Associated with homozygous mutations in the CASR gene
Urgent total parathyroidectomy (with autotransplantation and
cryopreservation) and thymectomy is indicated. Subtotal resection is
associated with high recurrence rates

28. SPECIAL CONDITIONS(contd.)
PERSISTANT AND RECURRENT HYPERPARATHYROIDISM
Persistence is defined as hypercalcemia that fails to resolve after
parathyroidectomy and is more common
Recurrence refers to HPT occurring after an intervening period of at least
6 months of biochemically documented normocalcemia
Ectopic parathyroids, unrecognized hyperplasia, supernumerary glands,
subtotal resection of a parathyroid tumor, parathyroid cancer, and
parathyromatosis

29. SPECIAL CONDITIONS(contd.)
RECURRENT OR PERSISTANT HPT
CONFIRM, RULE OUT BFHH,REVIEW OPERATIVE NOTES
NONINVASIVE LOCALISATION STUDIES
REDO/REMEDIAL
PARATHYROIDECTOMY
SELECTIVE VENOUS CATHETERISATION
LOCALISED
FU / MEDICAL

30. SPECIAL CONDITIONS(contd.)
HYPERCALCEMIA
Therapy of Primary Disease: Tumor resection (hypercalcemia of malignancy)
Parathyroidectomy (primary hyperparathyroidism)
Expansion of extracellular volume: Infusion of saline, Loop diuretics (furosemide)
Inhibition of Bone Resorption: Calcitonin, Glucocorticoids, Plicamycin (mithramycin),
Bisphosphonates, Gallium nitrate
Reduction of Intestinal Calcium Absorption: Low-calcium diet, Glucocorticoids
Other Treatments: Dialysis, Mobilization, Oral phosphate, Estrogens or progestogens
(postmenopausal women with PHPT), Chloroquine (sarcoidosis)

31. SPECIAL CONDITIONS(contd.)
HYPERCALCEMIC CRISIS:
Patients with primary HPT may occasionally present acutely with nausea,
vomiting, fatigue, muscle weakness, confusion and a decreased level
of consciousness; a complex referred to as hypercalcemic crisis.
Calcium levels are markedly elevated and may be as high as 16 to
20 mg/dL
Treatment consists of therapies to lower serum calcium levels followed by
surgery to correct hyperparathyroidism.The mainstay of therapy
involves rehydration with a 0.9% saline solution to keep urine output
greater than 100 mL/h. Once urine output is established, diuresis
with furosemide is begun. Furosemide works by increasing renal
calcium clearance, but should not be used without adequate
rehydration and salt loading

32. SPECIAL CONDITIONS(contd.)
SECONDARY HYPERPARATHYROIDISM
Commonly occurs in patients with chronic renal failure but may also
occur in those with hypocalcemia secondary to inadequate calcium or
vitamin D intake, or malabsorption
Abnormal parathyroid cell response to extracellular calcium or vitamin D
Surgical treatment is indicated and recommended for patients with bone
pain, pruritus, and (1) a calcium-phosphate product 70, (2) Ca
greater than 11 mg/dL with markedly elevated PTH, (3)
calciphylaxis, (4) progressive renal osteodystrophy, and (5) soft-
tissue calcification and tumoral calcinosis
Patients should undergo routine dialysis the day prior to surgery to
correct electrolyte abnormalities, especially in serum potassium
levels. A bilateral neck exploration is indicated

33. SPECIAL CONDITIONS(contd.)
TERTIARY HYPERPARATHYROIDISM:
Tertiary hyperparathyroidism is seen most commonly in patients with
long-standing renal dysfunction who undergo successful renal
transplantation. Generally, renal transplantation is an excellent
method of treating secondary HPT, but some patients develop
autonomous parathyroid gland function and tertiary HPT. Tertiary
HPT can cause problems similar to PHPT; The transplanted kidney is
also at risk
Operative intervention is indicated for symptomatic disease or if
autonomous PTH secretion persists for more than 1 year after a
successful transplant
The traditional surgical management of these patients consisted of
subtotal or total parathyroidectomy with autotransplantation

34. HYPOPARATHYROIDISM
 The parathyroid glands may be congenitally absent in the DiGeorge
syndrome, which also is characterized by lack of thymic
development, and, therefore, a thymus-dependent lymphoid system.
 Hyperparathyroidism in pregnant women can lead to
hypoparathyroidism in neonates from suppression of fetal
parathyroid tissue.
 By far, the most common cause of hypoparathyroidism is thyroid
surgery, particularly total thyroidectomy with a concomitant central
neck dissection. Patients often develop transient hypocalcemia as a
result of bruising or damage to the vascular supply of the glands;
permanent hypoparathyroidism is rare
 Presentation is with hypocalcemia

35. HYPOCALCEMIA
 Hypoparathyroidism:Surgical, Neonatal, Familial, Heavy metal
deposition, Magnesium depletion
 Resistance to the action of PTH: Pseudohypoparathyroidism, Renal
failure, Medications—calcitonin, bisphosphonates, mithramycin
 Failure of normal 1,25-dihydoxy vitamin D production
 Resistance to the action of 1,25-dihydroxy vitamin D
 Acute complex formation or deposition of calcium: Acute
hyperphosphatemia, Acute pancreatitis, Massive blood transfusion
(citrate overload), "Hungry bones"

36. HYPOCALCEMIA(contd.)
Neurologic : Circumoral paresthesia, Light-headedness, Depression,
Anxiety, Confusion, Chvostek's sign, Trousseau's sign, Irritability,
Laryngeal spasm, Seizures, Erb’s sign
Musculoskeletal: Tetany, Cramps, Involuntary twitching, Osteomalaciais
Cardiovascular: Electrocardiogram changes (prolonged QT interval, T-
wave peaking), Arrhythmia, Tachycardia, hypotension
Other Features: Lenticular cataracts

37. HYPOCALCEMIA(contd.)
SYMPTOM/GOAL TREATMENT
SYMPTOMATIC
HYPOCALCEMIA
Oral calcium carbonate or IV calcium gluconate
Vitamin D supplements to increase absorption
SYMPTOMATIC TETANY IV calcium gluconate ( 60 ml of 10% solution in 500 ml
D5% solution @ 1ml/kg/hr reviewed 4 hourly)
SYMPTOMATIC
HYPOMAGNESEMIA
IV Magnesium Chloride
VITAMIN D
SUPPLEMENTATION
Ergocalciferol, Calcifediol (liver disease), Calcitriol (renal
disease)
LONG TERM THERAPY Oral calcium carbonate, Low phosphate/ oxalate diet,
Parathyroid grafting (immunosuppressed or
cryopreserved)

38. ANY QUESTIONS ???

39. THANK YOU !