43

Hyperparathyroidism

317

Figure 43-1 Physiology of the Parathyroid Glands.

Key
Ca ! Calcium ions (Ca2 )

P ! Phosphate ions (HPO422)

H ! Hydroxyapatite

e
Bil

Vitamin D
enhances
absorption of
calcium and
phosphate:
Gastrointestinal
secretions
required for
this action

Kidney

Vit. D

Normal
Ca serum Ca
9 to 10.5
Ca
mg%

Ca

Ca

Cortisol
Opposes
Vit. D

Succus
entericus

P
P

Ca

Parathyroid
hormone
inhibits
reabsorption Ca
of P

Ca 3 P ! K

Ci
rcu ion
lat
Ca

Ca

Ca

H
H

Deposition of
Ca and P
promoted by
alkaline pH,
stress, anabolic
hormones, and
local tissue
concentration

Ca

H
H

H
H

Resorption of
calcium and
phosphate
stimulated by
parathyroid
hormone, by
acidosis and
citrate (?)
Osteoclast

H
H

Ca

Osteoclastic
and osteoblastic
activity in
dynamic
equilibrium

Osteoblast
P

H
H

Parathyroid
hormone
enhances
reabsorption
of Ca (secondary
action)

Ca

Acid
pH

normal adult
P serum level
40-150 U/L
Alkaline phosphatase

Stool
Normal excretion
on average diet
Ca
500 to 700 mg/24 hr
P
200 to 600 mg/24 hr
(30% of intake)

Ca

7
mg
%

P
Ca

Ca

Ca

Parathyroid hormone
promotes absorption of Ca

P
Alkaline
pH Alk. phosphatase

Calcium
excretion
controlled
by serum
threshold

Ca

Normal
P
adult
serum P P
3 to 4.5
mg% Regulatory mechanism

Gastric
acidity

Pancreatic
juice

Parathyroid
hormone

Inhibition

Stimulation

Gastrointestinal tract

Ca

H
H

H
H

H
H

Urine
Normal
excretion on
average diet
Ca!100 to 300
mg/24 hr
P!500 to 1000
mg/24 hr

H
H

H
H

Bone salts deposited as hydroxyapotite in proteinaceous bone matrix

Matrix growth requires protein, vitamin C, anabolic hormones (androgens, estrogen, IGF-1) stress of mobility
Matrix resorption favored by catabolic hormones (11-oxysteroids [cortisol], thyroid), parathyroid hormone immobilization

account for about 90% of cases of hypercalcemia. Malignancies include multiple myeloma, lymphomas, and prostate, breast, and squamous cell lung carcinomas. Malignant
tumors rarely secrete PTH, more often secreting PTHrelated peptide, which does not cross-react on the current
intact PTH assays. Certain medications cause hypercalcemia and may unmask underlying primary hyperparathyroidism. Thiazide diuretics decrease urinary calcium
excretion and may affect the responsiveness of target cells
to PTH. Lithium also increases urinary calcium retention

and may directly promote secretion of PTH. Additional

causes include other endocrine disorders (hyperthyroidism, primary adrenal insufficiency, and less commonly,
hypothyroidism and pheochromocytoma), milk alkali syndrome, excessive vitamin A or D intake, granulomatous
disorders (sarcoidosis, tuberculosis), and immobilization.
Generally, these conditions have suppressed PTH levels
and can be readily distinguished from primary hyperparathyroidism. Benign familial hypocalciuric hypercalcemia is
an autosomal dominant condition that causes asymptom-

318

SECTION V

Disorders of Endocrinology and Metabolism

Figure 43-2 Pathology and Clinical Manifestations of Hyperparathyroidism.

Strong
nails,
pseudoclubbing

Nephrocalcinosis
Increased flexibility of joints
Nephrolithiasis

Salt-and-pepper skull

Bone rarefaction;
cysts, fractures

Bone biopsy
(focal resorption)

Subperiosteal
resorption

Absence of lamina dura

(broken line indicates
normal contour)

Epulis (giant cell tumor)

Calcium deposits in blood vessels;

hypertension; heart failure

Codfishing of vertebrae

Multiple adenomas (pituitary,

thyroid, pancreas, adrenals)

Peptic
ulcer

Limbus keratopathy

atic hypercalcemia with low urinary calcium excretion

(<100 mg/day) and usually normal PTH levels. An inactivating mutation of the calcium receptor gene is the
common primary underlying abnormality that should be
suspected in individuals with a strong family history of
hypercalcemia. It is important to diagnose this condition
with a 24-hour urinary calcium measurement because
these individuals do not require any surgical therapy.
Secondary hyperparathyroidism occurs commonly but
is characterized by low or normal serum calcium levels.
The elevated PTH often occurs as a physiologic response
to conditions that cause hypocalcemia, such as vitamin D
deficiency and acute hyperphosphatemia (tumor lysis syn-

Pancreatitis

drome, acute renal failure, and rhabdomyolysis). It is seen

most commonly in renal insufficiency, particularly when
renal 1,25-dihydroxyvitamin D production is impaired,
with subsequent decreased intestinal calcium absorption.
In long-standing renal failure, the parathyroid glands
become autonomous, and a condition of tertiary hyperparathyroidism can develop, with PTH levels often greater
than 2 to 3 times normal.

Diagnostic Approach
The diagnosis of primary hyperparathyroidism is usually
straightforward and only requires the demonstration of