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Superior parathyroids
- 1) 4th pouch
- 2) associated with thyroid complex
- 3) lateral to recurrent laryngeal nerves (RLNs)
- 4) posterior surface of superior portion of the gland
- 4) above inferior thyroid artery
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Inferior parathyroids
- 1) 3rd pouch
- 2) associated with thymus
- 3) Medial to RLNs
- 4) more anterior
- 5) below inferior thyroid artery
- 6) inferior parathyroids have more variable location and are more likely to be ectopic
- 7) occasionally are found in the tail of the thymus (most common ectopic site) and can migrate to the anterior mediastinum
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Other ectopic sites of parathyroids:
- 1) intrathyroid
- 2) near tracheoesophageal groove
- 3) mediastinal
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What percentage of people have all 4 parathyroid glands?
90%
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What is the blood supply to the superior and inferior parathyroid glands
inferior thyroid artery
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PTH:
- 1) increases serum calcium
- 2) increases kidney calcium reabsorption in the distal convoluted tubule, decreases PO4 absorption
- 3) increases osteosclasts in bone to release Ca (and PO4-)
- 4) increased vitamin D production in kidney (increase 1-OH hydroxylation)--> increased Ca-binding protein in intestine--> increased intestinal Ca reabsorption
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Vitamin D
increases intestinal Ca and PO4 absorption by increasing calcium-binding protein
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Calcitonin
- 1) decreases serum calcium
- 2) decreases bone calcium resorption (inhibits osteoclasts)
- 3) increases urinary Ca and PO4- excretion
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Normal Ca level (total and ionized):
Normal PTH level:
Normal PO4 level:
Normal Cl- level:
- Normal Ca level (total and ionized): 8.5-10.5/4.4-5.5
- Normal PTH level: 5-40
- Normal PO4 level: 2.5-5
- Normal Cl- level: 98-107
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Whats the most common cause of hypoparathyroidism
previous thyroid surgery
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Primary hyperparathyroidism:
- 1) PRAD-1 oncogene increases the risk of adenomas
- 2) Women, older age
- 3) due to automomously high PTH
- 4) Dx:
- 1- increased Ca
- 2- decreased Phosphorous
- 3- Cl to phosphorous ratio >33
- 4- increased renal cAMP
- 5- HCO3- secreted in urine
- 5) can get hyperchloremic metabolic acidosis
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Osteitis fibrosa cystica (brown tumors)
bone lesions from Ca resorption, characteristic of hyperparathyroidism
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How does hyperparathyroidism present?
most patients have no symptoms- increased Ca found on routine lab work for some other problem or on checkup
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Symptoms of Hyperparathyroidism:
- 1) muscle weakness
- 2) myalgia
- 3) nephrolithiasis
- 4) pancreatitis
- 5) Peptic ulcer disease
- 6) depression
- 7) bone pain
- 8) pathologic fractures
- 9) mental status changes
- 10) constipation
- 11) nausea and vomiting
- 12) anorexia
- 13) hypertension can result from renal impairment
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Diagnositic workup for primary hyperparathyroidism
- 1) take careful history, including records of medications, symptoms, prior head and neck radiotherapy, and other endocrinopathies in the patient and the patient's family.
- 2) establish elevated calcium through 2 or 3 determinations
- 3) order a chest radiograph and search for bony metastases, sarcoidosis, and pulmonary tumors
- 4) order an excretory urogram and search for nephrolithiasis and rarely, renal tumors
- 5) order a serum protein electrophoresis to rule out multiple myeloma
- 6) order a 24-hour urinary calcium determination (benign familial hypocalciuric hypercalcemia)
- 7) rule out multiple endocrine neoplasia (usually MEN type I)
- 8) check the absolute or relative elevation of the PTH level.
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Surgical indications for primary hyperparathyroidism:
1) symptomatic disease
- 2) asymptomatic disease with:
- 1- Ca >13
- 2- decreased Cr clearance
- 3- kidney stones
- 4- substantialaly decreased bone mass
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What percentage of people with primary hyperparathyroidism have a single adenoma? Multiple adenomas? Diffuse hyperplasia
- Single adenoma- 80%
- Multiple adenomas- 4%
- Diffuse hyperplasia- 15%; patients with MENI or IIa have 4 gland hyperplasia
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Parathyroid adenocarcinoma:
very rare; can get very high Ca levels
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Treatment for primary hyperparathyroidism:
- Adenoma-
- 1) resection; inspect other glands to rule out hyperplasia or multiple adenomas
- Parathyroid hyperplasia-
- 1) do not biopsy all glands--> risks hemorrhage and hypoparathyroism.
- 2) Resect 3.5 glands or total parathyroidectomy and autoimplantation
- Parathyroid Ca1) need radical parathyroidectomy (need to take ipsilateral thyroid)
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hyperparathyroidism and preganancy?
surgery in 2nd trimester; increased risk of stillbirth if not resected
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How do you confirm that the tissue taken was indeed parathyroid?
intraop frozen section
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Intraop PTH levels
- 1) can help determine if the causative gland is removed (PTH should go to <1/2 the preop value)
- 2) PTH half-life is <10minutes
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Where should you look if you are missing a gland?
- 1) check inferiorly in thymus tissue (most commonly ectopic location)
- 2) near carotids
- 3) vertebral body
- 4) superior to pharynx
- 5) thyroid
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If you still cannot find gland:
- 1) close and follow PTH
- 2) if PTH still elevated, get parathyroid scan to localize
- 3) some say perform thyroidectomy on the side in which only one gland was found
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At reoperation for missing gland:
1) most common location for the gland is normal anatomic position
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Postop hypocalcemia-
- 1) caused by bone hunger
- 2) hypomagnesemia
- 3) failure of the parathyroid remnant or graft
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Persistent hyperparathyroidism -
(1%) most commonly due to a missed adenoma remaining in the neck
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Recurrent hyperparathyroidism:
- 1) occurs after a period of hypocalcemia or nornocalcemia
- 2) can be due to a new adenoma formation
- 3) can be due to tumor implants at the original operation that have now grown
- 4) need to consider recurrent parathyroid Ca
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What is reoperation associated with?
- 1- increased risk of RLN injury
- 2- permanent hypoparathyroidism
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Hypocalcemia postop:
- 1) Bone hunger- normal PTH, decreased HCO3-
- 2) Aparathyroidism- decreased PTH, normal HCO3-
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Sestamibi-technectium-99
- 1) will have preferential uptake by the overactive parathyroid gland
- 2) good for picking up adenomas but not 4-gland hyperplasia
- 3) best for trying to pick up ectopic glands
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Secondary hyperparathyroidism
- 1) seen in patients with renal failure
- 2) increased PTH in response to low Ca
- 3) most do not need surgery (90%)
- 4) ectopic calcification and osteoporosis can occur
- 5) Tx:
- 1- control diet PO4
- 2- PO4-binding gel
- 3- decrease aluminum
- 4- calcium supplement
- 5- vitamin D
- 6- calcium in dialysate
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When do you perform surgery in secondary hyperparathyroidism and what does the surgery involve?
- Surgery for:
- 1- bone pain ( most common indication; 80-90% get relief)
- 2- fractures
- 3- pruritis
2) surgery involves total parathyroidectomy with autotransplantation or subtotal parathyroidectomy
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Tertiary hyperparathyroidism
- 1) renal disease now corrected with transplant, but still overproducing PTH
- 2) has similar lab values as primary hyperparathyroisim (hyperplasia)
- 3) Tx:
- 1- subtotal (3.5 glands) or total parathyroidectomy with autoimplantation)
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Familial hypercalcemic hypocalciuria
- 1) patients have increased serum calcium and decreased urine calcium (should be increased if hyperparathyroidism)
- 2) caused by defect in PTH receptor in distal convoluted tubue of the kidney that causes increase resorption of calcium
- 3) Dx:
- 1- Calcium 9-11
- 2- normal PTH (30-60)
- 3- decreased urine Ca
- 4) Tx:
- 1- nothing (calcium generally not that high in these patients)
- 2- no parathyroidectomy
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Pseudohypoparathyroidism:
because of defect in PTH receptor in the kidney, does not respond to PTH
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Parathyroid cancer
- 1) rare cause of hypercalcemia
- 2) 50% 5 year survival rate
- 3) mortality is due to hypercalcemia
- 4) increased Ca, PTH, and alkaline phosphatase (can have extremely high Ca levels)
- 5) lung is most common location for metastases
- 6) Tx: wide en block excision (parathyroidectomy and ipsilateral thyroidectomy)
- 7) recurrence in 50%
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Multiple endocrine neoplasia syndromes
- 1) derviced from APUD cells (amine precursor uptake decarboxylase)
- 2) neoplasma can develop synchronously or metachronously
- 3) autosomal dominant, 100% penetrance, variable expressivity
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MEN I
- Pituitary Adenoma
- 1- prolactinoma #1
- 2- need to correct hyperparathyroidism 1st
- Parathyroid hyperplasia
- 1- usually the first part to become symptomatic; urinary symptoms
- 2- Tx: 4 gland resection with autotransplantation
- Pancreatic islet cell tumors
- 1- gastrinoma #1
- 2- 50% multiple, 50% malignant-major morbidity of syndrome
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MEN IIa
Parathyroid hyperplasia
- Medullary Ca of thyroid1- nearly all patients; diarrhea most common symptom; often bilateral
- 2- #1 cause of death in these patients
- 3- usually 1st part to be symptomatic
- 4- need to correct pheochromocytoma 1st
- Pheochromocytoma
- 1- very often bilateral, nearly always benign
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MEN IIb
- Pheochromocytoma
- 1- very often bilateral, nearly always benign
- Medullary Ca of thyroid
- 1- nearly all patients; diarrhea most common symptoms; often bilateral
- 2- #1 cause of death in these patients
- 3- usually 1st part to be symptomatic
- - Mucosal neuromas
- - Marfan's habitus, musculoskeletal abnormalities
Need to correct pheochromocytoma first
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Name the gene for MEN I:
MENIN gene
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Name the gene for MEN II
RET proto-oncogene
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See table on pg 145:
Disease Phenotypes Related to Mutation of the RET proto-oncogene
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Causes of Hypercalcemia
- 1) Malignancy
- 1- hematologic (25%)- lytic bone lesions
- 2- Nonhematologic (75%)- cancers release PTHrp (small cel lung Ca, breast Ca)
- 2) hyperparathyroidism
- 3) hyperthyroidism
- 4) familial hypercalcemic hypocalciuria
- 5) immobilization
- 6) granulomatous disease (sarcoidosis or tuberculosis)
- 7) excess vitamin D
- 8) milk-alkali syndome (excessive intake of milk and calcium supplements)
- 9) thiazide diuretics
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Mithramycin
- 1) inhibits osteoclasts (used with malignancies or failure of conventional treatment)
- 2) has hematologic, liver, and renal side effects
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Hyercalcemic crisis
- 1) usually secondary to another surgery
- 2) Tx:
- 1- fluids
- 2- furosemide
- 3- dialysis
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Breast Ca metastases to bone
- 1) release PTHrp; can cause hypercalcemia
- 2) small cell lung Ca and other nonhematologic cancers can do this as well--> this is not due to bone destruction
- 3) associated with increased urinary cAMP (from action of PTHrp on kidney
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Hematologic malignancies
1) these can cause bone destruction; can slo increase Ca and urinary cAMP will be low
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