Download Parathyroid gland and its related illnesses Parathyroid gland 4 small

Parathyroid gland and its related illnesses
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Parathyroid gland
4 small glands located on the dorsal side of the thyroid gland
Yellow brown
Ovoid or lentiform shape
Measure 3-10 mm x 2-6 mm x 1-4 mm
Weigh 50 mg each
Produces parathyroid hormone
Responsible for monitoring plasma Ca2+
Parathyroid gland
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Parathyroid hormone
A peptide hormone that increases plasma Ca2+
Released by chief cells
Chief cells contain receptors for Ca2+
A decrease in plasma Ca2+ levels mediates the release of PTH
Conversely, hypercalcemia inhibits PTH release
Parathyroid hormone
PTH causes increase in plasma Ca2+ by:
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Mobilization of Ca2+ from bone
Enhancing renal reabsorption
Increasing intestinal absorption (indirect)
Calcium metabolism
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Bone: main effect- stimulates osteoclasts -> bone breaks down -> Ca released
Intestines: increases uptake of Ca from intestine
Kidney: stimulates reabsorption of Ca from the Ca in kidney tubules
Calcium metabolism
Causes of hyperparathyroidism
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Parathyroid-related
-Primary hyperparathyroidism
-Lithium therapy
-Familial hypocalciuric hypercalcemia
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Malignancy-related
-Solid tumor with metastases (breast)
-Solid tumor with humoral mediation of hypercalcemia (lung, kidney)
-Hematologic malignancies (multiple myeloma, lymphoma, leukemia)
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Vitamin D-related
-Vitamin D intoxication
-↑ 1,25(OH)2D; sarcoidosis and other granulomatous diseases
-Idiopathic hypercalcemia of infancy
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Associated with high bone turnover
-Hyperthyroidism
-Immobilization
-Thiazides
-Vitamin A intoxication
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Associated with renal failure
-Severe secondary hyperparathyroidism
-Aluminum intoxication
-Milk-alkali
Primary hyperparathyroidism
Estimated incidence is 1 case per 1000 men and 2-3 cases per 1000 women
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Incidence increases above age 40
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Most patients with sporadic primary hyperparathyroidism are postmenopausal women with an
average age of 55 years
>80% of cases are caused by a solitary parathyroid adenoma
Approximately 10% are caused by double adenoma
Specific symptoms
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Clinical features of hyperparathyroidism
Osteitis fibrosa cystica
Nephrolithiasis
Pathologic fractures
Neuromuscular disease
Life-threatening hypercalcemia
Peptic Ulcer Disease
Non specific symptoms
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Fatigue
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Subjective muscle weakness
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Depression
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Increased thirst
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Polyuria
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Constipation
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Musculoskeletal aches and pains
Osteitis fibrosa cystica
Asociated syndromes with hyperparathyroidism
MEN I
MEN IIA
Familial Hypocalciuric Hypercalcemia
Hyperparathyroidism-jaw tumor syndrome
Fibro-osseous jaw tumors
Renal cysts
Solid renal tumors
Familial isolated hyperparathyroidism
MEN I
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1 in 30,000 persons
Features:
 Hyperparathyroidism (95%)
– Most common and earliest endocrine manifestation
 Gastrinoma (45%)
 Pituitary tumor (25%)
 Facial angiofibroma (85%)
 Collagenoma (70%)
Hyperparathyroidism in MEN I
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Early onset
Multiple glands affected
Post-op hypoparathyroidism more common (more extensive surgery)
Successful subtotal parathyroidectomy followed by recurrent HPT in 10 years in 50% of cases
MEN II
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Features:
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MTC(95%)
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Pheochromocytoma(50%)
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HPT(20%)
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RET mutation (98%)
1 in 30,000-50,000 people
Usually single adenoma but may have multi-gland hyperplasia
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Familial Hypocalciuric Hypercalcemia
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Benign condition
Autosomal dominant inherited disorder
Clinical features:
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hypocalciuria (usually < 50 mg/24 h)
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variable hypermagnesemia
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normal or minimally elevated levels of PTH
These patients do not normalize their hypercalcemia after subtotal parathyroid removal and should
not be subjected to surgery
Excellent prognosis
Diagnosed with family history and urinary calcium clearance determination
Secondary hyperparathyroidism
Decreased GFR leads to reduced inorganic phosphate excretion and consequent phosphate
retention
Retained phosphate has a direct stimulatory effect on PTH synthesis and on cellular mass of the
parathyroid glands
Retained phosphate also causes excessive production and secretion of PTH through lowering of
ionized Ca2+ and by suppression of calcitriol production
Secondary hyperparathyroidism
Reduced calcitriol production results both from decreased synthesis due to reduced kidney mass and
from hyperphosphatemia
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calcitriol is known to have a direct suppressive effect on PTH transcription and therefore
reduced calcitriol in CKD causes elevated levels of PTH
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Reduced calcitriol leads to impaired Ca2+ absorption from the GI tract, thereby leading to
hypocalcemia, which then increases PTH secretion and production
Tertiary hyperparathyroidism
Develops in patients with long-standing secondary hyperparathyroidism, which stimulates the growth
of an autonomous adenoma
A clue to the diagnosis of tertiary hyperparathyroidism is intractable hypercalcemia and/or an inability
to control osteomalacia despite vitamin D therapy
Investigations in hyperparathyroidism
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Primary HPT
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Increased serum calcium
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Phosphorus in low normal range
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Urinary calcium elevated
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Secondary HPT (renal etiology)
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Low or normal serum calcium
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High phosphorus
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Tertiary HPT (renal etiology)
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High calcium and phosphorus
Investigations in hyperparathyroidism
Intact PTH and chemistry panel
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PTH
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Calcium
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Phosphate
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Creatinine
24-hour urine calcium excretion
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Used to rule out familial hypocalciuric hypercalcemia
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Values below 100mg/24 hours or a calcium creatinine clearance ratio of <0.01 are suggestive
of FHH
Investigations in hyperparathyroidism
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Wrist, spine and hip dexa
Consider KUB, IVP or CT
Proper drug history
Hypoparathyroidism
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Lack of production of parathyroid hormone makes calcium levels in the blood low
and phosphorus levels high
This is a very rare condition, and almost always occurs because of damage or removal of parathyroid
glands at the time of parathyroid or thyroid surgery
Causes of hypoparathyroidism
Deficient Parathyroid Hormone (PTH) secretion (>99% of all cases)
Inability to make an active form of parathyroid hormone (extremely rare)
Inability of the kidneys & bones to respond to the parathyroid hormone being produced by normal
parathyroids (extremely rare)
Causes of hypoparathyroidism
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Isolated
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Autosomal dominant
• PTH gene mutation
• CASR activating mutation
• GCM2 mutation (dominant negative)
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Autosomal recessive
• PTH gene mutation
• GCM2 mutation
X-linked
Congenital multi-system syndromes
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DiGeorge & Velocardiofacial (22q11)
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Barakat/HDR
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Kenny-Caffey and Sanjad-Sakati
Causes of hypoparathyroidism
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Metabolic disease
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Mitochondrial neuromyopathies
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Long-chain hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency
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Heavy-metal storage disorders
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Autoimmune disease
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Autoimmune polyendocrine syndrome type I (APS-1 or APECED)
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Parathyroid resistance syndromes
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Pseudohypoparathyroidism
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Blomstrand chondrodysplasia and related PTH receptor defects
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Hypomagnesemia
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Muscle Cramps (spasms)
Dry Skin
Cataracts
Seizures
Pain in face, legs, feet
Abnormal teeth formation
Weakened tooth enamel
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Calcium
Phosphorous
PTH
Magnesium
Clinical features of hypoparathyroidism
Investigations in hypoparathyroidism