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.
ROS: Neg
PMH: None
PSH: None
Meds: None
Allergies: None
Social: No cigs, occasional EtOH, no drugs,
professional, weekend recreational soccer player.
Physical Exam
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
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
Chief Cells make PTH
Renal Effects of PTH
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
Increases bone resorption
Facilitates bone formation
Regulators of PTH
Calcium and Phosphate
Low Serum Ca2+
High Serum PO4 High Serum Ca2+
Low PO4
→
→
→
→
Increased PTH
Increased PTH
Decreased PTH
Decreased PTH
The most important regulator is Ca2+.
Pathophysiology of
Hyperparathyroidism
Parathyroid adenoma
A single adenoma is found
in 70-80% of primary
hyperparathyroidism.
Benign tumor.
Unregulated release of
PTH.
Double adenoma in 4-5%
Pathophysiology
Parathyroid hyperplasia
Diffuse enlargement of all
the parathyroid glands.
Unregulated release of
PTH.
10-15% of cases of primary
hyperparathyroidism.
Difficult operative
diagnosis.
Pathophysiology
Parathyroid carcinoma
Less than 1% of cases of hyperparathyroidism
Pathophysiology
Other etiologies
Multiple Endocrine Neoplasia Type 1 and 2
Abnormalities of thyroid, adrenal, and parathyroid glands
Hyperplasia of the parathyroid glands
Radiation therapy to the head and neck during
childhood for benign diseases.
Familial hyperparathyroidism has been observed
Rare.
Secondary Hyperparathyroidism
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
Hypercalcemia caused by autonomous
parathyroid function after long-term
hyperstimulation.
Differential Diagnosis of
Hypercalcemia
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
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
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
Clinical Presentation
Renal
Thirst
Polydipsia
Polyuria
Clinical Presentation
Gastrointestinal
Abdominal distress
Constipation
Vomiting
Anorexia
Weight loss
Clinical Presentation
Skeletal and neuromuscular
Bone pain and/or tenderness,
muscle fatigue, weakness
Spontaneous fractures
Clinical Presentation
Mental
Anxiety
Depression
Psychosis
Apathy
Fatigue
Clinical Presentations
Asymptomatic hypercalcaemia (50%)
Renal stones(28%)
Polyuria, polydipsia (5%)
Peptic ulcer (4%)
Hypertension(4%)
Bone disease(3%)
MEN 1 Syndrome(1%)
Workup
The diagnosis of hyperparathyroidism is made
by demonstrating elevated PTH in the setting of
high serum calcium.
Other Lab Findings
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…
141
103
12
124
4.1
19
Elevated PTH in
setting of elevated
Calcium
1.5
Decreased
Phosphorus
Decreased CO2.
Ca
Mg
Phos
PTH
11.0
2.4
0.8
81 (normal 0 - 50)
Complications of
Hyperparathyroidism
Chondrocalcinosis and pseudogout are common.
Significant loss of cortical bone.
Maternal hyperparathyroidism can lead to profound
hypocalcemia in newborns
Nocturia and polyuria
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:
Hypercalcemia-induced altered mental status
Osteitis Fibrosa Cystica
“Brown Tumor”
Indication of severe
disease.
Increased osteoclastic
resorption of calcified
bone with replacement
by fibrous tissue.
Treatment
Profound hypercalcemia with severe alterations
of mental status:
Normal saline and loop diuretics
Mild asymptomatic hypercalcemia:
Gentle Hydration
Treatment
Surgical removal of adenoma vs. conservative
for asymptomatic hyperparathyroidism.
For female patients who do not have surgery,
estrogen may be beneficial to help maintain
bone mass (controversial)
Treatment, Surgical
Guidelines for recommendation for surgical treatment
(from the 2002 NIH Workshop on Asymptomatic Primary
Hyperparathyroidism):
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
Avoid factors that can aggravate hypercalcemia:
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
Monitoring
Serum calcium every six months
Serum creatinine, and bone density (hip, spine, and
forearm) every 12 months.
Questions?