A 52-year-old female presents with nausea, fatigue, muscle weakness,
and intermittent pain in her left flank. Laboratory examination
reveals an increased serum calcium and a decreased serum phosphorus.
The patients plasma parathyroid hormone levels are increased, but
parathyroid hormonerelated peptide levels are within normal limits. Urinary
calcium is increased, and microhematuria is present. The patients
abnormality is most likely caused by
a. Primary hyperparathyroidism
b. Primary hypoparathyroidism
c. Pseudohypoparathyroidism
d. Secondary hyperparathyroidism
e. Secondary hypoparathyroidism
Cholera toxin causes massive and often fatal diarrhea by
a. Inactivating Gi protein
b. Irreversibly activating adenylate cyclase
c. Locking Gs protein into an inactive form
d. Rapidly hydrolyzing G protein GTP to GDP
e. Preventing GTP from interacting with G protein
answer:A
Hyperparathyroidism is caused by excess production of parathyroid
hormone (PTH). In patients with hyperparathyroidism, it is important to
distinguish primary hyperparathyroidism from secondary hyperparathyroidism.
Both forms may be associated with the development of bone
lesions, but excess PTH production in primary hyperparathyroidism leads
to different laboratory values than those seen with secondary hyperparathyroidism.
Increased levels of PTH in primary hyperparathyroidism
result in increased serum calcium (hypercalcemia) and decreased serum
phosphorus. The serum calcium levels are elevated because of increased
bone resorption and increased intestinal calcium absorption, the result of
increased activity of vitamin D. PTH also increases calcium reabsorption
in the distal renal tubule, but, because the filtered load of calcium exceeds
the ability for reabsorption, calcium is increased in the urine (hypercalciuria).
PTH also increases urinary excretion of phosphate. The excess calcium
in the urine predisposes to renal stone formation, especially calcium
oxalate or calcium phosphate stones. Urinary stones can produce flank
pain and hematuria. This is the most common presentation for patients
with hyperparathyroidism. The hypercalcemia of hyperparathyroidism
may also cause peptic ulcer disease due to the stimulation of gastrin
release and increased acid secretion from the parietal cells. The hypercalcemia
also results in muscle weakness, fatigue, and hypomotility of the GI
tract, which can lead to constipation and nausea. Alterations of mental status
are also common.
In contrast to primary hyperparathyroidism, secondary hyperparathyroidism
results from hypocalcemia. This causes secondary hypersecretion
of PTH and produces the combination of hypocalcemia and increased PTH
production. It is primarily found in patients with chronic renal failure.
Patients with hypoparathyroidism develop hypocalcemia and hyperphosphatemia
but have normal serum creatinine levels. Primary hypoparathy-
Endocrine System Answers 445
roidism and pseudohypoparathyroidism also result in decreased 24-h
excretion of calcium and phosphate.
ANSWER:B
Many extracellular substances cause intracellular actions via secondmessenger
systems. These second messengers may bind to receptors that
are located either on the surface of the cell or within the cell itself. Substances
that react with intracellular receptors are lipid-soluble (lipophilic)
molecules that can pass through the lipid plasma membrane. Examples of
these lipophilic substances include thyroid hormones, steroid hormones,
and the fat-soluble vitamins A and D. Once inside the cell these substances
generally travel to the nucleus and bind to the hormone response element
(HRE) of DNA.
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Some substances that react with cell surface receptors bind to guaninenucleotide
regulatory proteins. These proteins, called G proteins, may be
classified into four categories, namely Gs, Gi, Gt, and Gq. Two of these
receptors, Gs and Gi, regulate the intracellular concentration of cyclic
adenosine 5′-monophosphate (cAMP). In contrast, Gt regulates the intracytoplasmic
levels of cyclic guanosine 5′-monophosphate (cGMP), and Gq
regulates the intracytoplasmic levels of calcium ions. Gs and Gi regulate
intracellular cAMP levels by their actions on adenyl cyclase, an enzyme
located on the inner surface of the plasma membrane that catalyzes the formation
of cAMP from ATP. The adenylate cyclase G protein complex is
composed of the following components: the receptor, the catalytic enzyme
(i.e., adenyl cyclase), and a coupling unit. The coupling unit consists of
GTP-dependent regulatory proteins (G proteins), which may either be
stimulatory (Gs) or inhibitory (Gi). When bound to GTP and active, Gs
stimulates adenyl cyclase and increases cAMP levels. (Gs can be thought of
as the on switch.) In contrast, when bound to GTP and active, Gi inhibits
adenyl cyclase and decreases cAMP levels. (Gi can be thought of as the off
switch.) It is important to note that cholera toxin and pertussis toxin both
act by altering this adenyl cyclase pathway. Cholera toxin inhibits the conversion
of Gs-GTP to Gs-GDP. In contrast, pertussis toxin inhibits the activation
of Gi-GDP to Gi-GTP. Therefore, both cholera toxin and pertussis
toxin prolong the functioning of adenyl cyclase and therefore increase
intracellular cAMP, but their mechanisms are different. Cholera toxin keeps
the on switch in the on position, while pertussis toxin keeps the off
switch in the off position
