Transcript Document

Followup
Nathanael Wood, MD
December 20, 2005
CC: seizure-like activity
 HPI:
42 year old male was driving home after a soccer
game when his arms began shaking. He pulled
his car to the side of the road. When a police
officer found him he was unable to talk, with
rigid upper extremities. Symptoms lasted 15-20
minutes and began resolving spontaniously. He
remembers the entire event. When seen in the
ER, the patient was asymptomatic.
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ROS: Neg
PMH: None
PSH: None
Meds: None
Allergies: None
Social: No cigs, occasional EtOH, no drugs,
professional, weekend recreational soccer player.
Physical Exam
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T 98.8, HR 75, BP 135/85, RR 16, O2 sat 99%
General: age appropriate male in nad
HEENT: normal
CV: normal
Resp: normal
Abd: normal
Neuro: normal
Everything else: normal
Studies
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EKG: neg
Head CT: neg
Labs
141
103
12
124
4.1
Ca
Mg
Phos
PTH
19
11.0
2.4
0.8
81 (normal 0 - 50)
1.5
Hyperparathyroidism
Parathyroid Anatomy
Parathyroid Anatomy
Parathyroid Anatomy
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Chief Cells make PTH
Renal Effects of PTH
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Increases Ca2+ reabsorption in distal tubule
Decreases PO4- reabsorption in distal tubule
Increases 1-alpha-hydroxylase (which facilitates
the production of 1,25-(OH)2-Vit D)
Bone Effects of PTH
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Increases bone resorption
Facilitates bone formation
Regulators of PTH
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Calcium and Phosphate
Low Serum Ca2+
 High Serum PO4 High Serum Ca2+
 Low PO4
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→
→
→
→
Increased PTH
Increased PTH
Decreased PTH
Decreased PTH
The most important regulator is Ca2+.
Pathophysiology of
Hyperparathyroidism
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Parathyroid adenoma
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A single adenoma is found
in 70-80% of primary
hyperparathyroidism.
Benign tumor.
Unregulated release of
PTH.
Double adenoma in 4-5%
Pathophysiology
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Parathyroid hyperplasia
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Diffuse enlargement of all
the parathyroid glands.
Unregulated release of
PTH.
10-15% of cases of primary
hyperparathyroidism.
Difficult operative
diagnosis.
Pathophysiology
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Parathyroid carcinoma
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Less than 1% of cases of hyperparathyroidism
Pathophysiology
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Other etiologies
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Multiple Endocrine Neoplasia Type 1 and 2
Abnormalities of thyroid, adrenal, and parathyroid glands
 Hyperplasia of the parathyroid glands
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Radiation therapy to the head and neck during
childhood for benign diseases.
 Familial hyperparathyroidism has been observed
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Rare.
Secondary Hyperparathyroidism
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Occurs when the parathyroid glands become
hyperplastic after long-term stimulation to release PTH
in response to chronically low circulating calcium.
Chronic renal failure, rickets, and malabsorption
syndromes are the most frequent causes.
High levels of PTH do not cause hypercalcemia
because the primary problem is hypocalcemia.
With long-term hyperstimulation, the glands eventually
function autonomously and continue to produce high
levels of PTH even if the chronic hypocalcemia has
been corrected.
Tertiary Hyperparathyroidism
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Hypercalcemia caused by autonomous
parathyroid function after long-term
hyperstimulation.
Differential Diagnosis of
Hypercalcemia
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Primary hyperparathyroidism (more common in
out-patient)
Cancer (more common in in-patient)
Milk-alkali syndrome
Granulomatous disease
Hyperthyroidism
Drugs: thiazides, lithium
FHH (Familial hypocalciuric hypercalcemia)
Clinical Presentation of
Hyperparathyroidism
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Manifestations can be subtle
May run a benign course for many years
Less commonly, hyperparathyroidism may
worsen abruptly and cause severe hypercalcemic
complications (eg, profound dehydration,
neurologic symptoms, coma). This is referred to
as hypercalcemic parathyroid crisis.
Clinical Presentation of
Hypercalcemia
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At least half are asymptomatic
“Bones, Stones, Groans, and Psychic Moans”
Bones: Painful and tender bones
 Stones: Nephrolithiasis
 Groans: Abdominal pain
 Psychic Moans: Changes in mental status
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Clinical Presentation
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Renal
Thirst
 Polydipsia
 Polyuria
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Clinical Presentation
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Gastrointestinal
Abdominal distress
 Constipation
 Vomiting
 Anorexia
 Weight loss
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Clinical Presentation
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Skeletal and neuromuscular
Bone pain and/or tenderness,
muscle fatigue, weakness
 Spontaneous fractures
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Clinical Presentation
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Mental
Anxiety
 Depression
 Psychosis
 Apathy
 Fatigue
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Clinical Presentations
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Asymptomatic hypercalcaemia (50%)
Renal stones(28%)
Polyuria, polydipsia (5%)
Peptic ulcer (4%)
Hypertension(4%)
Bone disease(3%)
MEN 1 Syndrome(1%)
Workup
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The diagnosis of hyperparathyroidism is made
by demonstrating elevated PTH in the setting of
high serum calcium.
Other Lab Findings
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Elevated serum chloride levels.
Decreased serum phosphate level.
Decreased serum carbon dioxide
Hyperchloremic metabolic acidosis.
Increase in urine cyclic adenosine
monophosphate (cAMP).
Remember our patient…
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141
103
12
124
4.1
19
Elevated PTH in
setting of elevated
Calcium
1.5
Decreased
Phosphorus
 Decreased CO2.
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Ca
Mg
Phos
PTH
11.0
2.4
0.8
81 (normal 0 - 50)
Complications of
Hyperparathyroidism
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Chondrocalcinosis and pseudogout are common.
Significant loss of cortical bone.
Maternal hyperparathyroidism can lead to profound
hypocalcemia in newborns
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Nocturia and polyuria
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Can lead to tetany, coma, and death
neonatal severe hyperparathyroidism.
From the effects of calcium on the renal tubule.
Nephrolithiasis (20% of patients).
Most severe acute manifestation:
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Hypercalcemia-induced altered mental status
Osteitis Fibrosa Cystica
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“Brown Tumor”
Indication of severe
disease.
Increased osteoclastic
resorption of calcified
bone with replacement
by fibrous tissue.
Treatment
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Profound hypercalcemia with severe alterations
of mental status:
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Normal saline and loop diuretics
Mild asymptomatic hypercalcemia:
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Gentle Hydration
Treatment
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Surgical removal of adenoma vs. conservative
for asymptomatic hyperparathyroidism.
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For female patients who do not have surgery,
estrogen may be beneficial to help maintain
bone mass (controversial)
Treatment, Surgical
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Guidelines for recommendation for surgical treatment
(from the 2002 NIH Workshop on Asymptomatic Primary
Hyperparathyroidism):
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Patients with a serum calcium concentration of 1.0 mg/dL or more above the
upper limit of normal.
Patients with hypercalciuria.
Patients with a creatinine clearance that is 30 percent or lower than that of
age-matched normal subjects.
Patients with bone density at the hip, lumbar spine, or distal radius that is
more than 2.5 standard deviations below peak bone mass (T score <-2.5).
Patients who are less than 50 years old.
Patients in whom periodic follow-up will be difficult.
Treatment, Non-Surgical
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Avoid factors that can aggravate hypercalcemia:
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thiazide diuretic
lithium
volume depletion
prolonged bed rest or inactivity
high calcium diet
Encourage physical activity to minimize bone
resorption.
Encourage adequate hydration.
Maintain a moderate calcium intake (1000 mg/day).
Maintain moderate vitamin D intake.
Treatment, Non-Surgical
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Monitoring
Serum calcium every six months
 Serum creatinine, and bone density (hip, spine, and
forearm) every 12 months.
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Questions?