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Primary Hyperparathyroidism

Primary hyperparathyroidism is an endocrinological disorder characterized by an excess production of parathyroid hormone due to intrinsic alterations of the patient's parathyroid glands.


Presentation

Symptoms presented by patients suffering from PHPT result from excess mobilization of osseous calcium phosphate and hypercalcemia. Colloquially, they are often summed up with "stones, bones, abdominal groans and psychic moans" or similar expressions.

Here, stones refers to nephrolithiasis, nephrocalcinosis and nephrogenic diabetes insipidus. Patients may report polyuria and consecutive polydipsia. In severe cases, renal failure may occur.

PHT stimulates osteoclast activity and continuously increased levels of this hormone lead to loss of bone mass. Osteitis fibrosa cystica is classically associated with PHPT and is characterized by replacement of decomposed bone with fibrous tissue. Cysts are recognizable on radiographic images and may turn into so-called brown tumors, which are not true neoplasms. Osteopenia, osteoporosis and osteomalacia have also been described in PHPT patients.

Hypercalcemia stimulates gastrin and subsequently gastric acid production. Therefore, nausea, vomiting, peptic ulcers and abdominal pain are common symptoms of PHPT [10]. Constipation is frequently observed but does not seem to be triggered by hypercalcemia [11]. In some case, PHPT has been related to pancreatitis.

Electrolyte imbalances presumably also account for neuropsychiatric symptoms. Patients may present with reduced awareness, memory impairment, depression or psychosis.

Additionally, malaise, fatigue and muscle weakness are characteristic for this disease.

Fatigue
  • We present a case of a 54-year-old woman with fatigue, myalgia, and poor concentration who was found to have hypercalcemia (corrected calcium, 11.2 mg/dL) and elevated parathyroid hormone level (112 pg/mL), laboratory values consistent with primary hyperparathyroidism[ncbi.nlm.nih.gov]
  • She suffered from thirst and fatigue for one month. Her serum calcium (a) levels were 19.0 mg/dL, and she was diagnosed with hypercalcemic crisis. Circulating levels of parathyroid and thyroid hormones were elevated.[ncbi.nlm.nih.gov]
  • A 46 year-old female patient presented to the hospital with ongoing and progressively increasing fatigue, severe nausea and vomiting, loss of appetite, constipation, palpitations and somnolence.[ncbi.nlm.nih.gov]
  • Symptoms of primary hyperparathyroidism (PHP), namely fatigue, lethargy and proximal muscle weakness, are unspecific and could be mistaken as complaints naturally present during pregnancy. Thus, diagnosis is usually delayed.[ncbi.nlm.nih.gov]
  • She presented with fatigue, myalgias, cramps and paraesthesia. Her physical examination was normal.[ncbi.nlm.nih.gov]
Nausea
  • A 46 year-old female patient presented to the hospital with ongoing and progressively increasing fatigue, severe nausea and vomiting, loss of appetite, constipation, palpitations and somnolence.[ncbi.nlm.nih.gov]
  • Most common adverse events were nausea and vomiting, especially at the beginning of therapy; however, only one patient withdrew from the study because of adverse events.[ncbi.nlm.nih.gov]
  • Signs and symptoms include weakness, fatigue, nausea, vomiting, constipation, depression, bone pain, osteoporosis, cystic bone lesions, and kidney stones Applies To Hyperplasia of parathyroid ICD-9-CM Volume 2 Index entries containing back-references[icd9data.com]
  • Two weeks later, he was re-admitted with diffuse musculoskeletal soreness, anorexia, constipation, nausea, and localized abdominal pain and multiple osteolytic lesions on plain radiographs.[ncbi.nlm.nih.gov]
  • "Abdominal groans" may be uttered because of nausea, vomiting, gastric ulcers, constipation and abdominal pain.[symptoma.com]
Vomiting
  • A 46 year-old female patient presented to the hospital with ongoing and progressively increasing fatigue, severe nausea and vomiting, loss of appetite, constipation, palpitations and somnolence.[ncbi.nlm.nih.gov]
  • A 30-year-old Caucasian woman booked under Consultant care presented at 32 weeks gestation with vomiting and right-sided loin pain. Following presentation, she was diagnosed with renal calculi.[ncbi.nlm.nih.gov]
  • Most common adverse events were nausea and vomiting, especially at the beginning of therapy; however, only one patient withdrew from the study because of adverse events.[ncbi.nlm.nih.gov]
  • Signs and symptoms include weakness, fatigue, nausea, vomiting, constipation, depression, bone pain, osteoporosis, cystic bone lesions, and kidney stones Applies To Hyperplasia of parathyroid ICD-9-CM Volume 2 Index entries containing back-references[icd9data.com]
  • He presents three months symptoms of constipation, anorexia, vomiting and weight loss.[pesquisa.bvsalud.org]
Abdominal Pain
  • Here, a 32 years old lady with burning to colicky recurrent upper abdominal pain, polyuria, polydipsia associated with anorexia, dyspepsia, generalized body ache, joint pain, constipation and weight loss has been described.[ncbi.nlm.nih.gov]
  • Hyperparathyroidism can become apparent early in its course when a patient presents with symptoms of abdominal pain, recurrent renal calculi, repeated fractures, or behavior changes.[ncbi.nlm.nih.gov]
  • Two weeks later, he was re-admitted with diffuse musculoskeletal soreness, anorexia, constipation, nausea, and localized abdominal pain and multiple osteolytic lesions on plain radiographs.[ncbi.nlm.nih.gov]
  • "Abdominal groans" may be uttered because of nausea, vomiting, gastric ulcers, constipation and abdominal pain.[symptoma.com]
  • Symptoms: Fatigue Fractures Decreased height Upper abdominal pain Loss of appetite Nausea Muscular weakness Muscle pain Depression Personality changes Stupor and possibly coma Kidney stones Increased urination Signs and tests: Radioimmunoassay of parathyroid[uclahealth.org]
Loss of Appetite
  • A 46 year-old female patient presented to the hospital with ongoing and progressively increasing fatigue, severe nausea and vomiting, loss of appetite, constipation, palpitations and somnolence.[ncbi.nlm.nih.gov]
  • Symptoms of too much calcium in the blood may include: Constipation Frequent urination Increased thirst Joint pain Kidney pain (due to the presence of kidney stones) Lack of energy and extreme tiredness (fatigue) Loss of appetite Muscle weakness Other[saintlukeshealthsystem.org]
  • Symptoms: Fatigue Fractures Decreased height Upper abdominal pain Loss of appetite Nausea Muscular weakness Muscle pain Depression Personality changes Stupor and possibly coma Kidney stones Increased urination Signs and tests: Radioimmunoassay of parathyroid[uclahealth.org]
  • Excess PTH causes GI symptoms like nausea, vomiting, abdominal pain, and loss of appetite. Finally, the psychic groans of the saying stem from hypercalcemia's effect on neurotransmitters. This can cause symptoms like depression and memory problems.[study.com]
  • They may be associated with fatigue, muscle weakness, loss of appetite, nausea, peptic ulcers and neuropsychiatric symptoms. No preventive measures can be recommended against sporadic PHPT.[symptoma.com]
Polydipsia
  • Here, a 32 years old lady with burning to colicky recurrent upper abdominal pain, polyuria, polydipsia associated with anorexia, dyspepsia, generalized body ache, joint pain, constipation and weight loss has been described.[ncbi.nlm.nih.gov]
  • "Stones" refers to kidney stones, nephrocalcinosis, and diabetes insipidus (polyuria and polydipsia). These can ultimately lead to renal failure. "Bones" refers to bone-related complications.[en.wikipedia.org]
  • Patients may report polyuria and consecutive polydipsia. In severe cases, renal failure may occur. PHT stimulates osteoclast activity and continuously increased levels of this hormone lead to loss of bone mass.[symptoma.com]
  • Osteitis fibrosa cystica [described in pathophysiology, almost obsolete now] Urinary Symptoms Increase in volume of urine – polyuria [due to hyperphosphaturia] Increased thirst of water – polydipsia [due to hyperphosphaturia] Renal calculi Nephrocalcinosis[boneandspine.com]
  • Cardiovascular disease Left ventricular hypertrophy Arterial hypertension Shortened QT interval Kidney Nephrolithiasis, nephrocalcinosis Polyuria, polydipsia Musculoskeletal system Bone, muscle, and joint pain Pseudogout Osteitis fibrosa cystica ( cyst-like[amboss.com]
Hypertension
  • RESULTS: Baseline data of normotensive and essential hypertension patients were matched for age, sex, BMI and 24-h ambulatory blood pressure monitoring values with normotensive and hypertensive-primary hyperparathyroidism patients, respectively.[ncbi.nlm.nih.gov]
  • Primary aldosteronism (PA) represents the main cause of endocrine secondary arterial hypertension in which aldosterone production is inappropriately elevated.[ncbi.nlm.nih.gov]
  • Three of these patients had no history of hypertension.[doi.org]
  • Maternal complications of primary hyperparathyroidism include nephrolithiasis, pancreatitis, cardiac arrhythmias, hypertension and peptic ulcers. At its most severe, hypercalcaemic crisis may occur, presenting with acute neurological disturbance.[ncbi.nlm.nih.gov]
  • Prior myocardial infarction, hypertension, cardiac failure, arrhythmia, cancer, fracture, and ulcer were associated with an increased risk of death (see 4 ).[doi.org]
Osteopenia
  • [ edit ] Osteopenia and bone demineralization are present in all forms of hyperparathyroidism Subperiosteal.[en.wikibooks.org]
  • These days, the most common radiologic finding in primary hyperparathyroidism is osteopenia, which may be generalized or asymmetric. Fine trabeculations are initially lost, with resultant coarse and thickened trabeculae.[emedicine.com]
  • This leads to porous, brittle bones known as osteopenia and osteoporosis. Continue on to Part 2 of the interview, which covers the complications, personal experiences, medications and advice for primary hyperparathyroidism![healthcentral.com]
  • Osteopenia, osteoporosis and osteomalacia have also been described in PHPT patients. Hypercalcemia stimulates gastrin and subsequently gastric acid production.[symptoma.com]
  • The fundamental skeletal radiologic manifestation include diffuse osteopenia, pathologic fractures and the coexistence of resorption and sclerosis at numerous sites.[en.wikipedia.org]
Bone Pain
  • We present the case of 48 year-old women, admitted with intense bone pain, headache and dizziness. Imaging studies performed identified a small nodule localized in the anterior mediastinum.[ncbi.nlm.nih.gov]
  • Signs and symptoms include weakness, fatigue, nausea, vomiting, constipation, depression, bone pain, osteoporosis, cystic bone lesions, and kidney stones Applies To Hyperplasia of parathyroid ICD-9-CM Volume 2 Index entries containing back-references[icd9data.com]
  • Clinical Findings [ edit ] The classic medical school clinical findings are "Stones, Bones, abdominal moans, and psychiatric overtones," referring to renal calculi, bone pain, peptic ulcers, pancreatitis, and CNS symptoms (confusion lethargy, weakness[en.wikibooks.org]
  • Signs and Symptoms of PHPT Mild Fatigue (feeling very tired) Depression Anxiety General aches and pains Flank pain or blood in the urine from kidney stones Severe Nausea and vomiting Bone pain Increased thirst and urination Constipation Forgetfulness[hormone.org]
  • Patients experience brittle, fractured or broken bones and bone pain. The other symptoms in the saying come from hypercalcemia.[study.com]
Muscle Weakness
  • Symptoms of primary hyperparathyroidism (PHP), namely fatigue, lethargy and proximal muscle weakness, are unspecific and could be mistaken as complaints naturally present during pregnancy. Thus, diagnosis is usually delayed.[ncbi.nlm.nih.gov]
  • Maternal symptoms include: hyperemesis, muscle weakness, pancreatitis, nephrolithiasis, bone disease, mental status changes, and hypercalcaemic crisis. Untreated disease complicates foetal development and foetal death is a significant risk.[ncbi.nlm.nih.gov]
  • CASE REPORT During her second pregnancy, a 28-year-old woman presented with symptoms of general weakness, bone and joint pain, multiple fractures with bone deformity, muscle weakness, and gait disturbance.[ncbi.nlm.nih.gov]
  • Symptoms of too much calcium in the blood may include: Constipation Frequent urination Increased thirst Joint pain Kidney pain (due to the presence of kidney stones) Lack of energy and extreme tiredness (fatigue) Loss of appetite Muscle weakness Other[saintlukeshealthsystem.org]
  • They may be associated with fatigue, muscle weakness, loss of appetite, nausea, peptic ulcers and neuropsychiatric symptoms. No preventive measures can be recommended against sporadic PHPT.[symptoma.com]
Back Pain
  • Clinical presentations included neck and low back pain, radicular pain, paraparesis, and sphincter dysfunction. Surgical removal of the spine lesions was achieved in all cases. Spine fusion and instrumentation was done in 3 cases.[ncbi.nlm.nih.gov]
  • Dauphine RT, Riggs BL, Scholz DA. 1975 Back pain and vertebral crush fractures: an unrecognized mode of presentation for primary hyperparathyroidism. Ann Intern Med 83:365–367. PubMed Google Scholar 27.[doi.org]
  • X-ray or VF assessment of spine if clinically indicated (height loss or back pain). 4. Creatinine clearance and serum creatinine annually. 5.[f1000research.com]
Polyuria
  • Here, a 32 years old lady with burning to colicky recurrent upper abdominal pain, polyuria, polydipsia associated with anorexia, dyspepsia, generalized body ache, joint pain, constipation and weight loss has been described.[ncbi.nlm.nih.gov]
  • "Thrones" refers to polyuria and constipation "Psychiatric overtones" refers to effects on the central nervous system.[en.wikipedia.org]
  • Systemic signs: renal (polyuria, hypercalciuria, nephrolithiasis) skeletal, neuromuscular (myopathy, chondrocalcinosis, arthritis), central nervous system (fatigue, cognitive changes), gastrointestinal (peptic ulcer, pancreatitis), cardiovascular (hypertension[iofbonehealth.org]
  • Patients may report polyuria and consecutive polydipsia. In severe cases, renal failure may occur. PHT stimulates osteoclast activity and continuously increased levels of this hormone lead to loss of bone mass.[symptoma.com]
  • Osteitis fibrosa cystica [described in pathophysiology, almost obsolete now] Urinary Symptoms Increase in volume of urine – polyuria [due to hyperphosphaturia] Increased thirst of water – polydipsia [due to hyperphosphaturia] Renal calculi Nephrocalcinosis[boneandspine.com]
Confusion
  • We conclude that parathyroid adenomas, although uncommon in children, are an important cause of skeletal disease that may initially be confused with hypovitaminosis D.[ncbi.nlm.nih.gov]
  • When large, these masses of cystic fibrous tissue are termed "Brown Tumors" as they may be confused with neoplasms.[pathwaymedicine.org]
  • Clinical Findings [ edit ] The classic medical school clinical findings are "Stones, Bones, abdominal moans, and psychiatric overtones," referring to renal calculi, bone pain, peptic ulcers, pancreatitis, and CNS symptoms (confusion lethargy, weakness[en.wikibooks.org]
  • It can cause a variety of symptoms, including: frequent urination stomach problems confusion fatigue Primary hyperparathyroidism occurs when your parathyroid glands produce too much PTH.[healthline.com]
  • Signs and Symptoms of PHPT Mild Fatigue (feeling very tired) Depression Anxiety General aches and pains Flank pain or blood in the urine from kidney stones Severe Nausea and vomiting Bone pain Increased thirst and urination Constipation Forgetfulness Confusion[hormone.org]
Headache
  • We present the case of 48 year-old women, admitted with intense bone pain, headache and dizziness. Imaging studies performed identified a small nodule localized in the anterior mediastinum.[ncbi.nlm.nih.gov]
  • These chapters eloquently describe how patients present with common clinical conditions, such as headache, fever, cough, palpitations, or anemia, and provide an overview of typical symptoms, physical findings, and differential diagnosis.[worldcat.org]
  • Preoperatively, non-specific symptoms were common: anxiety, body pain, abdominal distention, forgetfulness, headaches, and mood swings. Significant improvement in quality of life was found 3, 6, and 12 months after surgery.[f1000research.com]

Workup

Laboratory analyses of blood samples typically reveal increased levels of PTH, hypercalcemia, hypophosphatemia and augmented alkaline phosphatase levels. Serum 25-hydroxyvitamin D concentrations are not altered in PHPT. Urine analysis shows high levels of phosphate and most commonly elevated levels of calcium. The extent of abnormal findings does not necessarily correlate with severity of symptoms [11].

Patients may present comorbidities and employ medication to treat them. Distinct compounds may modulate calcium homeostasis and simulate PHPT. Thiazide diuretics reduce renal calcium excretion and lead to increased serum calcium levels. If at all possible, such medication should be stopped two weeks before obtaining blood and urine samples from a patient suspicious for hyperparathyroidism. Other iatrogenic causes of hypercalcemia are long-term lithium treatment, tamoxifen administration and intake of oral contraceptives.

In order to diagnose PHPT, repeated measurements have to be performed and pathological findings need to be reproducible. This is of particular importance since any deviation from the characteristic pattern of findings may indicate another disease. Secondary hyperparathyroidism, for instance, is related to hypocalcemia and hyperphosphatemia but also to augmented PTH concentrations. Vitamin D deficiencies or renal insufficiency may account for these symptoms. Tertiary hyperparathyroidism is associated with increased levels of PTH, hypercalcemia and hyperphosphatemia.

Diagnostic imaging is not required for diagnosing PHPT. However scintigraphy may be very helpful to localize the lesion and to distinguish single tumors from hyperplasia or multiple adenomas and this information is of great value when preparing minimally invasive surgery [12]. Indeed, lack of response to minimally invasive surgery commonly results from undetected multiple parathyroid gland involvement. Scintigraphic examination may be combined with sonography or magnetic resonance imaging.

Additionally, pre-operative bone scans not only allow for an assessment of osseous lesions, but also permit an estimation of post-operative hypocalcemia. They may also provide important information to support a decision for or against surgery [13].

Nephrolithiasis
  • It is not uncommon, patient with parathyroid adenoma come to health care professionals with the chief complain of recurrence nephrolithiasis.[ncbi.nlm.nih.gov]
  • Seventy-eight patients (34%) had a baseline calcium 11.2 mg/dL, but compared with patients with calcium 11.2 mg/dL, only the incidence of nephrolithiasis was more common in those patients with significant hypercalcemia (18% vs 9%, p 0.04).[ncbi.nlm.nih.gov]
  • Although primary hyperparathyroidism (PHPT) is asymptomatic in most patients, its main clinical manifestation is nephrolithiasis. In general, hypercalcemia would lead to unilateral renal stones, which may become bilateral over time.[ncbi.nlm.nih.gov]
  • Maternal symptoms include: hyperemesis, muscle weakness, pancreatitis, nephrolithiasis, bone disease, mental status changes, and hypercalcaemic crisis. Untreated disease complicates foetal development and foetal death is a significant risk.[ncbi.nlm.nih.gov]
  • We present the case of a 75-year-old woman with a 10 year history of nephrolithiasis and severe osteoporosis, with multiple fragility fractures. Her bone and kidney status required a more thorough metabolic assessment.[ncbi.nlm.nih.gov]
Schmorl's Nodes
  • Structural weakening of the vertebral bodies can permit herniation into the disk space (Schmorl's nodes). Schmorl's nodes are sometimes widespread in die spines of patients with hyperparathyroidism.[healio.com]
Parathyroid Hormone Increased
  • When released, parathyroid hormone increases the release of calcium from the bone, reabsorption from the kidney, and secondarily stimulates absorption of calcium from the intestines. It also stimulates secretion of phosphate in the kidney.[en.wikibooks.org]
  • Because parathyroid hormone increases calcium release from bones, primary hyperparathyroidism can lead to low bone mineral density or osteoporosis and increased risk of bone fractures.[yourhormones.info]
  • Excess parathyroid hormone increases osteoclastic activity and bone turnover which causes osteopenia and osteoporosis.[clinicaladvisor.com]
Short QT Interval
  • Also, manifestations related to symptomatic hypercalcemia can be present; these include nausea, vomiting, constipation, polyuria, polydipsia, mental confusion, coma, and a short QT interval on the electrocardiogram 20.[f1000research.com]

Treatment

Watchful waiting is indicated for asymptomatic patients with mild electrolyte imbalances, conserved renal function and minimal loss of bone mass. These patients should, however, undergo regular follow-ups to detect disease progress as early as possible. In this line, blood samples should be analyzed twice a year for calcium and phosphate levels as well as renal parameters. Bone scans should be performed in longer intervals. In order to delay or avoid disease progress, treatment of comorbidities with medication that aggravates hypercalcemia should be re-considered, possibly reduced or replaced. Patients should be advised to maintain appropriate hydration and to keep a diet with moderate calcium content. About 1 g per day is recommended. These measures may help to prevent nephrolithiasis without stimulating PTH production. Physical activity is highly recommended to strengthen the muscles that support the weakened skeleton.

Mild cases may also indicate drug therapy. Electrolyte imbalances should be adjusted and such measures will also protect the kidneys. Osseous lesions may be treated with inhibitors of bone resorption, e.g. with biphosphonates.

Symptomatic patients are usually recommended for surgery. Parathyroidectomy is the treatment of choice and should be carried out after localizing all sites of tissue alterations. Single adenoma may be resected in a minimally invasive approach, but this is often not possible in case of hyperplasia or multiple adenomas. Here, open surgery needs to be carried out. It is not necessary to remove parathyroid glands that don't show any pathological alteration.

Parathyroidectomy is considered a safe and successful surgical procedure. Cure rates exceed 95% and complications rarely occur. Post-operative hypocalcemia is likely, but more frequently result from bone repair processes than from an absolute lack of PTH. Hemorrhages have been described and patients may claim transient raucousness.

Of note, ectopic parathyroid tumors have been reported. If PTH levels do not drop after parathyroidectomy, the possibility of ectopic, endocrinologically active tissues should be considered. They may be identified in imaging studies and require surgical removal. They are not necessarily located in close proximity to the parathyroid and thyroid glands.

Follow-ups consist in analyses of blood samples to assure physiological serum levels of PTH and electrolytes as well as bone density measurement about one year after surgery.

Prognosis

In general, prognosis for PHPT is good. Parathyroidectomy is the treatment of choice to normalize electrolyte concentrations and bone density, is related to high cure rates, but may not even be required in asymptomatic patients [8] [9]. Regular follow-ups should be realized to detect possible disease progress if an initial decision against surgical intervention is taken. Age seems to be a favorable prognostic factor and young patients are at higher risk of disease progress and the need for parathyroidectomy.

Electrolyte imbalances may trigger fatal cardiovascular accidents.

Etiology

The majority of PHPT cases, an estimated 85%, is caused by a single parathyroid adenoma. A significant share of patients, approximately 15% of all cases, presents with hyperplasia or multiple adenomas. Parathyroid cancer is rare and seems to account for about 1% of PHPT cases [2].

The etiology of parathyroid tumors and hyperplasia is not fully understood. Genetic predisposition and epigenetic mechanisms have been proposed to increase the individual risk of developing sporadic PHPT [1]. In contrast, high familial incidence does definitely result from genetic disorders. In this context, the disease may be diagnosed in patients suffering from familial isolated hyperparathyroidism, hyperparathyroidism-jaw tumor syndrome, familial benign hypocalciuric hypercalcemia and its more severe, homozygous form neonatal severe hyperparathyroidism [3], or any multiple endocrine neoplasia syndrome.

Epidemiology

Data regarding incidence and prevalence of the disease may be underestimated due to an unknown, but presumably high number of asymptomatic patients [4]. Keeping this limitation in mind, the annual incidence of PHPT has been estimated to be about 2 per 10,000 individuals [5]. While the overall prevalence amounts to approximately 0.1%, there are significant differences between males and females. Prevalence in women is up to 4-fold higher than prevalence in men. Indeed, postmenopausal women account for the greatest share of patients and PHPT is the most common cause for hypercalcemia in this group of patients [6]. PHPT may rarely be diagnosed in children and adolescents. Most patients are diagnosed with this endocrinological disorder during their sixth decade of life.

Sex distribution
Age distribution

Pathophysiology

Under physiological conditions, calcium, phosphate and regulatory hormone concentrations are tightly regulated. Negative feedback is the main mechanism behind such regulation and in this context, PTH expression and release should diminish upon:

These are precisely the effects of PTH production stimulation.

In PHPT, down-regulation of PTH synthesis is impaired. Parathyroid tumors presumably present anomalies in sensing serum calcium levels or in intracellular transduction pathways. In cases of parathyroid hyperplasia, an abnormally high number of endocrinologically active cells seems to contribute to PHPT symptoms, too.

PTH counteracts low calcium levels by mobilization of calcium phosphate from osseous tissue. Although this assures rapid elevation of available calcium amounts, in the long term, it will cause osteopenia. In PHPT patients, extensive loss of bone mass cannot be compensated by calcitriol-mediated bone formation. In severe cases, affected individuals may develop osteitis fibrosa cystica.

Continuously increased serum calcium levels combined with an enhanced re-absorption in distal tubuli of the kidney may lead to exceedance of the solubility products of calcium salts and subsequent formation of renal calculi.

Hypercalcemia and hypophosphatemia are characteristic yet not specific for PHPT. They may be associated with fatigue, muscle weakness, loss of appetite, nausea, peptic ulcers and neuropsychiatric symptoms [7].

Prevention

No preventive measures can be recommended against sporadic PHPT. Family members of patients suffering from genetic disorders triggering hyperparathyroidism may benefit from regular blood analyses in order to detect pathological alterations early.

Summary

The parathyroid gland is a paired, endocrinological organ. Its name derives from its close proximity to the thyroid gland, although both organs work independently. The main function of the parathyroid gland is the synthesis and release of parathyroid hormone (PTH), one of the main modulators of calcium homeostasis.

In detail, PTH synthesis is stimulated by decreased serum calcium levels and elevated phosphate concentrations. The hormone induces rapid mobilization of calcium phosphate from the bones by increasing osteoclast activity. On the other hand, it augments calcium re-absorption and diminishes phosphate recovery in renal tubuli. Both processes contribute not only to augmented calcium availability, but also provoke a shift in calcium to phosphate ratios and thus further increase serum levels of unbound, ionized calcium.

PTH synthesis decreases to basal levels if serum calcium concentrations are in their physiological range. Also, it promotes calcitriol synthesis and calcitriol, in turn, inhibits PTH production. Calcitriol enhances intestinal calcium and phosphate absorption and stimulates bone formation. These regulatory mechanisms prevent an excess production of PTH, hypercalcemia, hypophosphatemia and loss of bone mass.

However, if regulation fails because of primary hyperparathyroidism (PHPT), i.e., because of an intrinsic lesion of the parathyroid gland, these pathological conditions will manifest. The precise combination of altered endocrinological and electrolyte parameters allows diagnosis of PHPT and helps to distinguish this disease from secondary or other forms of hyperparathyroidism. Neoplasms, mainly benign adenoma, are the main causes of PHPT. Furthermore, genetic predisposition and irradation may account for this disease or contribute to tumor development [1].

Patient Information

The parathyroid glands are small, endocrinologically active organs in close proximity to the thyroid gland. Their main functions are synthesis and release of parathyroid hormone (PTH). This hormone plays a major role in maintaining calcium homeostasis. In detail, PTH is stimulated by low serum calcium levels and counteracts by rapidly mobilizing osseous calcium phosphate and by decreasing renal calcium excretion and phosphate recovery.

Under normal circumstances, this results in physiological calcium and phosphate concentrations that inhibit further PTH synthesis by means of negative feedback mechanisms. However, in cases of primary hyperparathyroidism (PHPT), these regulatory mechanisms do not work very well because PTH production persists independent of inhibitory factors.

Causes

The vast majority of PHPT patients suffers from either a single or multiple benign tumors of the parathyroid glands. Less than 1% of all cases results from a malignant neoplasm of this organ.

In rare cases, genetic disorders account for this disease.

Symptoms

Because the above described regulatory mechanisms fail, PHPT patients present with elevated PTH levels, increased serum calcium concentrations, diminished phosphate levels and osseous lesions. They are often summed up in the expression "stones, bones, abdominal groans and psychic moans":

Diagnosis

Diagnosis of PHPT is based on the results of blood and urine samples. Measurements have to be repeated in order to avoid erroneous diagnoses due to momentary hormonal or electrolyte imbalances.

Scintigraphic examinations may be carried out to localize and quantify parathyroid lesions.

Treatment

Mild, asymptomatic cases may just require regular follow-ups to detect possible disease progress as early as possible. Drug therapy may be employed to correct electrolyte imbalances, to prevent renal disorders and for inhibition of bone resorption.

Patients presenting with symptoms of low bone density or hypercalcemia are usually recommended for surgical resection of altered parathyroid tissue. In many cases, this surgical intervention can be realized with minimally invasive techniques.

References

Article

  1. Westin G. Molecular genetics and epigenetics of nonfamilial (sporadic) parathyroid tumours. J Intern Med. 2016.
  2. Barazeghi E, Gill AJ, Sidhu S, et al. 5-Hydroxymethylcytosine discriminates between parathyroid adenoma and carcinoma. Clin Epigenetics. 2016; 8:31.
  3. Waller S, Kurzawinski T, Spitz L, et al. Neonatal severe hyperparathyroidism: genotype/phenotype correlation and the use of pamidronate as rescue therapy. Eur J Pediatr. 2004; 163(10):589-594.
  4. Silverberg SJ, Bilezikian JP. The diagnosis and management of asymptomatic primary hyperparathyroidism. Nat Clin Pract Endocrinol Metab. 2006; 2(9):494-503.
  5. Wermers RA, Khosla S, Atkinson EJ, et al. Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993-2001: an update on the changing epidemiology of the disease. J Bone Miner Res. 2006; 21(1):171-177.
  6. Lundgren E, Hagstrom EG, Lundin J, et al. Primary hyperparathyroidism revisited in menopausal women with serum calcium in the upper normal range at population-based screening 8 years ago. World J Surg. 2002; 26(8):931-936.
  7. Jorde R, Waterloo K, Saleh F, Haug E, Svartberg J. Neuropsychological function in relation to serum parathyroid hormone and serum 25-hydroxyvitamin D levels. The Tromso study. J Neurol. 2006; 253(4):464-470.
  8. Udelsman R, Donovan PI. Open minimally invasive parathyroid surgery. World J Surg. 2004; 28(12):1224-1226.
  9. Silverberg SJ, Bilezikian JP. The diagnosis and management of asymptomatic primary hyperparathyroidism. Nat Clin Pract Endocrinol Metab. 2006; 2(9):494-503.
  10. Gardner EC, Jr., Hersh T. Primary hyperparathyroidism and the gastrointestinal tract. South Med J. 1981; 74(2):197-199.
  11. Bargren AE, Repplinger D, Chen H, Sippel RS. Can biochemical abnormalities predict symptomatology in patients with primary hyperparathyroidism? J Am Coll Surg. 2011; 213(3):410-414.
  12. Hindie E, Ugur O, Fuster D, et al. 2009 EANM parathyroid guidelines. Eur J Nucl Med Mol Imaging. 2009; 36(7):1201-1216.
  13. Castellano E, Attanasio R, Gianotti L, Cesario F, Tassone F, Borretta G. Forearm Dxa Increases the Rate of Patients with Asymptomatic Primary Hyperparathyroidism Meeting Surgical Criteria. J Clin Endocrinol Metab. 2016:jc20161513.

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Last updated: 2019-07-11 20:24