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Parathyroid Gland

There are 4 tiny, pea-sized parathyroid glands embedded into the thyroid gland - one attached to the top and one attached to the bottom of each thyroid lobe. 

Primary Hyperparathyroidism

Primary hyperparathyroidism (pHPT) is the inappropriate excess production of parathyroid hormone.  The term hyperparathyroidism was first coined in the 1920s to describe a syndrome characterized by bone disease, renal stones, fatigue, hypercalcemia and high urine calcium.  The diagnosis was dependent on symptoms related to “bones, stones, abdominal groans and moans” which often correlated with severe bone disease, advanced kidney disease, psychiatric and neuromuscular disorders respectively. The symptoms were often associated with evidence of calcification of the kidneys, bone erosion of the fingers, boney tumors and changes in the appearance of the skull on X-ray. 
Over the years our understanding of calcium metabolism has improved, and the disease has changed so that currently the definition of pHPT like the current commonest presentation of pHPT, is biochemical: hypercalcemia (high blood calcium) in the presence of an absolute or relative inappropriately elevated PTH level.  The disease now covers a spectrum that has extremes as diverse as asymptomatic normocalcemic hyperparathyroidism to hypercalcemic crises. 
Primary hyperparathyroidism is the commonest cause of hypercalcemia (high blood calcium) in the community.  The prevalence of pHPT in the US is approximately 3/1000,  it is twice as common in females as males, and increases with advancing age in both sexes.
“Asymptomatic” Primary Hyperparathyroidism
Whilst most patients currently diagnosed with pHPT are described as asymptomatic, the myriad of subtle clinical symptoms including malaise, fatigue, depression, memory loss, poor concentration, loss of libido, increased thirst (polydipsia), frequent urination (polyuria), constipation, nonspecific bone and joint aches are very common.  Health related quality of life scores are reduced in apparently asymptomatic patients and they improve following surgery (parathyroidectomy).  Furthermore, asymptomatic pHPT is associated with higher rates of hypertension, high blood fats, insulin resistance, unfavorable body fat distribution, cardiac and vascular dysfunction, and morbidity from cardiovascular diseases.
Symptomatic Primary Hyperparathyroidism
Amongst patients with symptomatic disease kidney stones are the commonest clinical feature.
Bone disease (low bone density and osteoporosis) is common but less frequently associated with fractures than in the past.
Gastrointestinal symptoms resulting from smooth muscle relaxation include constipation, anorexia, nausea and vomiting. Hypercalcemia increases gastric acid secretion and may account for ulcer disease (which overall is now uncommon).
Hypercalcemic Crisis
A hypercalcemic crisis is an uncommon condition that occurs in no more than 1-2% of pHPT.  It is characterized by a serum calcium that is very high (greater than 12mg/dL) and is typically associated with a rapid deterioration in central nervous system, cardiac, gastrointestinal and renal function. 

Normocalcemic Hyperparathyroidism
Patients with normocalcemic hyperparathyroidism are normocalcemic but with a consistently inappropriately elevated PTH in the absence of secondary causes of hyperparathyroidism.  The significance of this condition is controversial but once secondary causes of PTH elevation have been excluded there is a suggestion that it may represent the earliest form of pHPT, a phase characterized by elevated PTH that leads to a reduced cortical bone density but without hypercalcemia. The second phase of pHPT is defined by the development of hypercalcemia and therefore leads to the investigation and diagnosis.
The treatment of normocalcemic pHPT remains controversial because the emergence of clinical features of pHPT is unpredictable as is the evolution to a hypercalcemic state. The fact that some patients remain normocalcemic despite the clinical manifestations of pHPT inevitably raises the question of the definition of a ‘normal’ serum calcium level for an individual patient.  Each patient has to be assessed and treated on their specific merits.

Parathyroid surgery

Parathyroidectomy – surgery to remove a parathyroid gland - is currently the only available definitive cure for primary hyperparathyroidism. It is known to improve the bone, abdominal and urological effects associated with primary hyperparathyroidism. It frequently also improves the more subtle symptoms that often co-exist including fatigue, memory loss and reduced concentration. As a consequence, surgery is usually recommended in all patients with primary hyperparathyroidism that have symptoms. Reliable preoperative localization studies including sestamibi scanning, high resolution ultrasound and 4D CT scanning permits the identification of the diseased parathyroid gland in the majority of cases, so most patients are candidates for a minimally invasive parathyroidectomy.

Primary Hyperparathyroid
Parathyroid surgery
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