Hyperparathyroidism
Overactivity of the parathyroid glands resulting in excess production of parathyroid
hormone (PTH). The parathyroid hormone regulates and maintains calcium and
phosphate levels. Overactivity of one or more of the parathyroid glands causes high
calcium levels (hypercalcemia) and low levels of phosphate in the blood
PTH works in 3 ways, increases metabolism of vitamin D into it’s active form
(therefore increasing calcium absorption from the gut), decreasing excretion of
calcium from the kidneys and increasing osteoclast activity (therefore increaseing
calcium resorption from bone).
Classification
Primary hyperparathyroidism
Primary hyperparathyroidism results from a hyperfunction of the parathyroid glands
themselves. There is oversecretion of PTH due to adenoma, hyperplasia or, rarely,
carcinoma of the parathyroid glands.
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The most common cause is a benign parathyroid adenoma that loses its
sensitivity to circulating calcium levels. Usually, only one of the four
parathyroid glands is affected.
A less common cause is from multiple endocrine neoplasia (MEN).
Secondary hyperparathyroidism
Secondary hyperparathyroidism is the reaction of the parathyroid glands to a
hypocalcemia caused by something other than a parathyroid pathology, e.g. chronic
renal failure. The bone disease in secondary parathyroidism along with renal failure is
termed renal osteodystrophy.
In chronic renal failure, phosphate is not as easily excreted, which leads to
hyperphosphataemia. This increased phosphate binds to free calcium forming calcium
phosphate, which is unusable to the body – leading to decreasing calcium levels. Also,
since vitamin D is converted into its active form in the kidney, CRF results in ↓ active
Vit D, which ↓ calcium absorption from the gut.
The net overall effect is ↑ phosphate and ↓ calcium with ↑ PTH as the parathyroids try
to compensate for the hypocalcaemia by releasing more PTH. However the PTH can
not fully compensate for the hypocalcaemia so you will have hypocalcaemia with
hyperparathyroidism.
Tertiary hyperparathyroidism
Tertiary hyperparathyroidism is a state of excessive secretion of parathyroid hormone
(PTH) after a long period of secondary hyperparathyroidism and resulting in
hypercalcemia. In cases of long-standing secondary hyperparathyroidism, the
hypertrophied parathyroid glands can become autonomously functioning and continue
to secrete PTH independent of whether the original stimuli to secrete PTH are still
present.
Symptoms
Asymptomatic hyperparathyroidism
Diagnosis made on further investigation after a coincidental finding of hypercalcemia.
Symptomatic hyperparathyroidism
Symptoms are commonly associated with the effects of hypercalcaemia. Since
calcium is involved in trans-synaptic communication within our nervous system, high
blood calcium levels have a direct effect on the nervous system. Thus, most of the
symptoms of parathyroid disease are "neurological" in origin. The most common
symptom is fatigue and tiredness. Other very common symptoms are
lack of energy
memory problems
concentration
sleep disturbance
depression
Other manifestations of hyperparathyroidism usually involve the kidney (stones) and
the skeletal system (bone pain due to the development of osteoporosis).
The symptoms of hyperparathyroidism can be remembered by the rhyme "moans,
groans, stones, bones, and psychiatric overtones":
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"moans" (complaints of not feeling well)
"groans" (abdominal pain, gastroesophageal reflux)
"stones" (kidney)
"bones" (bone pain)
"psychiatric overtones" (lethargy, fatigue, depression, memory problems).
Other symptoms include: weight loss, myopathy, constipation, headaches,
gastroesophageal reflux causing dysphagia, decreased sex drive, thinning hair, AF.
Additional symptoms reported consist of an increased thirst (polydipsia) and urination
(polyuria) as a result of calcium excretion in the urine, and if neglected, renal
impairment due to nephrocalcinosis followed by renal failure.
Laboratory tests
Serum calcium
In cases of primary, tertiary hyperparathyroidism increased PTH consequently leads
to increased serum calcium (hypercalcemia) due to:
1. increased bone resorption, allowing flow of calcium from bone to blood
2. reduced renal clearance of calcium
3. increased intestinal calcium absorption
By contrast, in secondary hyperparathyroidism effectiveness of PTH is reduced.
Serum phosphorus
In primary hyperparathyroidism, serum phosphorus levels are abnormally low as a
result of decreased renal tubular phosphorus reabsorption. This contrasts with
secondary hyperparathyroidism, in which serum phosphorus levels are generally
elevated because of renal disease.
Calcium Pathway
Alkaline phosphatase
Alkaline phosphatase levels are not elevated in all types of hyperparathyroidism.
Kumar and Clark 6 Edition states that alkaline phosphatase levels do not increase in
primary Hyperparathyroidism but may increase in secondary Hyperparathyroidism.
Diagnosis
The gold standard of diagnosis is the PTH immunoassay. Once an elevated PTH has
been confirmed, goal of diagnosis is to determine whether the hyperparathyroidism is
primary or secondary in origin by obtaining a serum calcium level:
PTH serum calcium likely type
high high
primary hyperparathyroidism
high low or normal secondary hyperparathyroidism
Tertiary hyperparathyroidism has a high PTH and a high serum calcium. It is
differentiated from primary hyperparathyroidism by a history of chronic kidney
failure and secondary hyperparathyroidism.
Treatment and monitoring
Treatment is first and foremost directed at hypercalcemia, symptomatic patients are
sent for surgery to remove the parathyroid tumor (parathyroid adenoma).
Treatment
Treatment is usually surgical removal of the gland(s) containing adenomas.
Medications
Medications include estrogen replacement therapy in postmenopausal women and
bisphosphonates.
Surgery
Surgery reduces all cause mortality as well as resolving symptoms. A consensus
statement in 2002 recommended the following indications for surgery in
asymptomatic hyperparathyroidism:
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Serum calcium (above upper limit of normal): 2.6mmol/L
24-h urinary calcium >400 mg
Creatinine clearance reduced by 30% compared with age-matched subjects.
Bone mineral density t-score <−2.5 at any site
Age <50
However, if surgery is not available, the following should be monitored:
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Calcium level: via urine tests. The results can be used to provide information
regarding kidney functionality as well as how much calcium is being excreted
in your urine.
Bone density: bone mineral density tests – risk of osteoporosis. (DEXA)
Abdominal X-rays can be used to check for kidney stones.
Prevention
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Exercise, specifically weight and strength training are beneficial. This helps in
the process of decreasing bone loss and building stronger bones.
Vitamin D - Adequate amounts of vitamin D aid in calcium absorption.
Sources of vitamin D come from the foods you eat, sunlight, and from vitamin
supplements.
Stay hydrated to prevent the formation of kidney stones.
No smoking - Besides known negative effects of smoking such as cancer,
smoking aids in bone loss