Hyperparathyroidism

Primary hyperparathyroidism
From Wikipedia, the free encyclopedia

Classification and external resources

Thyroid and parathyroid.
ICD-10
E21.0
ICD-9
252.01
DiseasesDB
6283
eMedicine
radio/355
MeSH
D049950

Primary hyperparathy-
roidism causes hypercalcemia (elevated blood calcium levels) through the excessive secretion of parathyroid hormone (PTH), usually by an adenoma (benign tumors) of the parathyroid glands. Its incidence is approximately 42 per 100,000 people. It is almost exactly three times as common in women as men.

Signs and Symptoms
The signs and symptoms of primary hyperparathyroidism are those of hypercalcemia. They are classically summarized by the mnemonic "stones, bones, abdominal groans and psychic moans".

1. "Stones" refers to kidney stones, nephrocalcinosis, and diabetes insipidus (polyuria and polydipsia). These can ultimately lead to renal failure.
2. "Bones" refers to bone-related complications. The classic bone disease in hyperparathyroidism is osteitis fibrosa cystica, which results in pain and sometimes pathological fractures. Other bone diseases associated with hyperparathyroidism are osteoporosis, osteomalacia, and arthritis.
3. "Abdominal groans" refers to gastrointestinal symptoms of constipation, indigestion, nausea and vomiting. Hypercalcemia can lead to peptic ulcers and acute pancreatitis.
4. "Psychic moans" refers to effects on the central nervous system. Symptoms include lethargy, fatigue, depression, memory loss, psychosis, ataxia, delirium, and coma.
5. Left ventricular hypertrophy.[1]
6. Increased all cause mortality [2]

Other signs include proximal muscle weakness, itching, and band keratopathy of the eyes.

Diagnosis
The diagnosis of primary hyperparathyroidism is made by blood tests.

1. Serum calcium levels are elevated.
2. The serum chloride phosphate ratio is 33 or more in most patients with primary hyperparathyroidism. [3][4][5] However, thiazide medications have been reported to causes ratios above 33.[6]

Urinary cAMP is occasionally measured; this is generally elevated.

Parathyroid hormone activity
Intact PTH levels are also elevated.

Causes
The most common cause of primary hyperparathyroidism is a sporadic, single parathyroid adenoma resulting from a clonal mutation (~97%). Less common are hyperplasia of all parathyroid glands (~2.5%), parathyroid carcinoma (malignant tumor), and adenomas in more than one gland (together ~0.5%). Primary hyperparathyroidism is also a feature of several familial endocrine disorders: Multiple endocrine neoplasia type 1 and type 2A (MEN type 1 and MEN type 2A), and familial hyperparathyroidism.
In all cases, the disease is idiopathic, but is thought to involve inactivation of tumor suppression genes(Menin gene in MEN1), or involve gain of function mutations (RET proto-oncogene MEN 2a).

Complications
The classic bone disease in hyperparathyroidism is osteitis fibrosa cystica, which results in pain and sometimes pathological fractures. Other bone diseases associated with hyperparathyroidism are osteoporosis, osteomalacia, and arthritis.

Treatment
Treatment is usually surgical removal of the gland(s) containing adenomas.

Medications
Medications include estrogen replacement therapy in postmenopausal women and bisphosphonates. Bisphosphonates may improve bone turnover.[7] Newer medications termed "calcimimetics" used in secondary hyperparathyroidism are now being used in Primary hyperparathyroidism. Their benefits are as yet unclear.

Surgery
The symptoms of the disease, listed above, are indications for surgery. Surgery reduces all cause mortality as well as resolving symptoms. However, cardiovascular mortality is not significantly reduced[8]

A consensus statement in 2002 recommended the following indications for surgery in asymptomatic hyperparathyroidism[9]:

• Serum calcium (above upper limit of normal): 1.0 mg/dl
• 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>

More recently, randomized controlled trials have studied the role of surgery in patients with asymptomatic hyperparathyroidism. The largest study reported that surgery showed increase in bone mass, but no improvement in quality of life after one to two years among patients with[10]:

• Untreated, asymptomatic primary hyperparathyroidism
• Serum calcium between 2.60 - 2.85 mmol/liter (10.4 - 11.4 mg/dl)
• Age between 50 and 80 yr
• No medications interfering with Ca metabolism
• No hyperparathyroid bone disease
• No previous operation in the neck
• Creatinine level <>

Two other trials reported improvements in bone density and some improvement in quality of life with surgery.[11][12]

Future therapies
Future developments such as calcimemetic agents (e.g. cinacalcet) which activate the parathyroid calcium-sensing receptor may offer a good alternative to surgery.

See also
Secondary hyperparathyroidism
Tertiary hyperparathyroidism

References

1. ^ Stefenelli T, Abela C, Frank H, et al (1997). "Cardiac abnormalities in patients with primary hyperparathyroidism: implications for follow-up". J. Clin. Endocrinol. Metab. 82 (1): 106–12. PMID 8989242.
2. ^ Vestergaarde and Mosekilde, BMJ Cohort study on effects of parathyroid surgery on multiple outcomes in primary hyperparathyroidism.2003 Sep 6;327(7414):530-4.Click here to read
3. ^ Reeves CD, Palmer F, Bacchus H, Longerbeam JK (1975). "Differential diagnosis of hypercalcemia by the chloride/phosphate ratio". Am. J. Surg. 130 (2): 166–71. PMID 1155729.
   This study found a ratio above 33 to have a sensitivity of 94% and a specificity of 96%.
4. ^ Palmer FJ, Nelson JC, Bacchus H (1974). "The chloride-phosphate ratio in hypercalcemia". Ann. Intern. Med. 80 (2): 200–4. PMID 4405880.
5. ^ Broulík PD, Pacovský V (1979). "The chloride phosphate ratio as the screening test for primary hyperparathyroidism". Horm. Metab. Res. 11 (10): 577–9. PMID 521012.
   This study found a ratio above 33 to have a sensitivity of 95% and a specificity of 100%.
6. ^ Lawler FH, Janssen HP (1983). "Chloride:phosphate ratio with hypercalcemia secondary to thiazide administration". The Journal of family practice 16 (1): 153–4. PMID 6848626.
7. ^ Khan AA, Bilezikian JP, Kung AW, et al (2004). "Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial". J. Clin. Endocrinol. Metab. 89 (7): 3319–25. doi:10.1210/jc.2003-030908. PMID 15240609.
8. ^ Vestergaarde and Mosekilde, BMJ Cohort study on effects of parathyroid surgery on multiple outcomes in primary hyperparathyroidism.2003 Sep 6;327(7414):530-4
9. ^ Bilezikian JP, Potts JT, Fuleihan Gel-H, et al (2002). "Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century". J. Clin. Endocrinol. Metab. 87 (12): 5353–61. PMID 12466320.
10. ^ Bollerslev J, Jansson S, Mollerup CL, et al (2007). "Medical observation, compared with parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial". J. Clin. Endocrinol. Metab. 92 (5): 1687–92. doi:10.1210/jc.2006-1836. PMID 17284629.
11. ^ Ambrogini E, Cetani F, Cianferotti L, et al (2007). "Surgery or surveillance for mild asymptomatic primary hyperparathyroidism: a prospective, randomized clinical trial". J. Clin. Endocrinol. Metab. 92 (8): 3114–21. doi:10.1210/jc.2007-0219. PMID 17535997.
12. ^ Rao DS, Phillips ER, Divine GW, Talpos GB (2004). "Randomized controlled clinical trial of surgery versus no surgery in patients with mild asymptomatic primary hyperparathyroidism". J. Clin. Endocrinol. Metab. 89 (11): 5415–22. doi:10.1210/jc.2004-0028. PMID 15531491.
    

v • d • eEndocrine pathology: endocrine diseases (E00-35, 240-259)
Thyroid
Hypothyroidism (Iodine deficiency, Cretinism, Congenital hypothyroidism, Goitre, Myxedema) - Hyperthyroidism (Graves disease, Toxic multinodular goitre, Teratoma with thyroid tissue or Struma ovarii) - Thyroiditis (De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's thyroiditis) - Euthyroid sick syndrome - Thyroid hormone resistance
Pancreas
Diabetes mellitus (type 1, type 2, coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy, MODY) - Hypoglycemia - Hyperinsulinism - Zollinger-Ellison syndrome - insulin receptor (Rabson-Mendenhall syndrome)
Parathyroid
Hypoparathyroidism (Pseudohypoparathyroidism) - Hyperparathyroidism (Primary, Secondary, Tertiary)
Pituitary
Hyperpituitarism (Acromegaly, Hyperprolactinaemia, SIADH) - Hypopituitarism (Simmonds' disease/Sheehan's syndrome, Kallmann syndrome, Growth hormone deficiency, Diabetes insipidus) - Adiposogenital dystrophy - Empty sella syndrome - Pituitary apoplexy - Adrenocorticotropic hormone deficiency
Adrenal
Cushing's syndrome (Nelson's syndrome, Pseudo-Cushing's syndrome) - CAH (Lipoid, 3β, 11β, 17α, 21α) - Hyperaldosteronism (Conn syndrome, Bartter syndrome) - Adrenal insufficiency (Addison's disease) - Hypoaldosteronism
Gonads
ovarian dysfunction (Polycystic ovary syndrome, Premature ovarian failure) - testicular dysfunction (5-alpha-reductase deficiency) - testosterone biosynthesis (17-beta-hydroxysteroid dehydrogenase deficiency) - general (Hypogonadism, Delayed puberty, Precocious puberty)

Other
Androgen insensitivity syndrome - Autoimmune polyendocrine syndrome - Carcinoid syndrome - Gigantism - Short stature (Laron syndrome, Psychogenic dwarfism) - Multiple endocrine neoplasia (1, 2) - Progeria - Woodhouse-Sakati syndrome

Retrieved from "http://en.wikipedia.org/wiki/Primary_hyperparathyroidism"
Categories: Endocrinology

For information on another disease, click on Pancreatitis SOD Library

Seconday Hyperparathyroidism

Secondary hyperparathyroidism
From Wikipedia, the free encyclopedia

Classification and external resources

Thyroid and parathyroid.
ICD-10
E21.1
ICD-9
252.02, 588.81
DiseasesDB
6301
MeSH
D006962

Secondary hyperparathyroidism refers to the excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia (low blood calcium levels) and associated hypertrophy of the glands. This disorder is especially seen in patients with chronic renal failure. It is often--although not consistently--abbreviated as SHPT in medical literature.

Signs and Symptoms
Bone and joint pain are common, as are limb deformities. The elevated PTH has also pleiotropic effects on blood, immune system and neurological system.

Diagnosis
The PTH is elevated due to decreased levels of calcium or 1,25-dihydroxy-vitamin D3. It is usually seen in cases of chronic renal disease or defective calcium receptors on the surface of parathyroid glands.

Causes
Chronic renal failure is the most common cause of secondary hyperparathyroidism. Failing kidneys do not convert enough vitamin D to its active form, and they do not adequately excrete phosphorus. When this happens, insoluble calcium phosphate forms in the body and removes calcium from the circulation. Both processes leads to hypocalcemia and hence secondary hyperparathyroidism. Secondary hyperparathyroidism can also result from malabsorption (chronic pancreatitis, small bowel disease) in that the fat soluble vitamin D can not get reabsorbed. This leads to hypocalcemia and a subsequent increase in parathyroid hormone secretion in an attempt to increase the serum calcium levels.

Treatment
If the underlying cause of the hypocalcemia can be addressed, the hyperparathyroidism will resolve. In patients with chronic renal failure, older treatments consists of dietary restriction of phosphorus, supplements with the active form of vitamin D (Paricalcitol), and phosphate binders. In recent years, a newer class of medications, calcimimetics cinacalcet, have achieved amazing response rates and has reduced the number of patients who eventually require surgery. Some of these patients may also see resolution of their sHPT following kidney transplantation.

Prognosis
If left untreated, the disease will progress to tertiary hyperparathyroidism, where correction of the underlying cause will not stop excess PTH secretion, i.e. parathyroid gland hypertrophy becomes irreversible.

See also
Primary hyperparathyroidism
Tertiary hyperparathyroidism

v • d • eEndocrine pathology: endocrine diseases (E00-35, 240-259)

Thyroid
Hypothyroidism (Iodine deficiency, Cretinism, Congenital hypothyroidism, Goitre, Myxedema) - Hyperthyroidism (Graves disease, Toxic multinodular goitre, Teratoma with thyroid tissue or Struma ovarii) - Thyroiditis (De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's thyroiditis) - Euthyroid sick syndrome - Thyroid hormone resistance

Pancreas
Diabetes mellitus (type 1, type 2, coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy, MODY) - Hypoglycemia - Hyperinsulinism - Zollinger-Ellison syndrome - insulin receptor (Rabson-Mendenhall syndrome)

Parathyroid
Hypoparathyroidism (Pseudohypoparathyroidism) - Hyperparathyroidism (Primary, Secondary, Tertiary)

Pituitary
Hyperpituitarism (Acromegaly, Hyperprolactinaemia, SIADH) - Hypopituitarism (Simmonds' disease/Sheehan's syndrome, Kallmann syndrome, Growth hormone deficiency, Diabetes insipidus) - Adiposogenital dystrophy - Empty sella syndrome - Pituitary apoplexy - Adrenocorticotropic hormone deficiency

Adrenal
Cushing's syndrome (Nelson's syndrome, Pseudo-Cushing's syndrome) - CAH (Lipoid, 3β, 11β, 17α, 21α) - Hyperaldosteronism (Conn syndrome, Bartter syndrome) - Adrenal insufficiency (Addison's disease) - Hypoaldosteronism

Gonads
ovarian dysfunction (Polycystic ovary syndrome, Premature ovarian failure) - testicular dysfunction (5-alpha-reductase deficiency) - testosterone biosynthesis (17-beta-hydroxysteroid dehydrogenase deficiency) - general (Hypogonadism, Delayed puberty, Precocious puberty)

Other
Androgen insensitivity syndrome - Autoimmune polyendocrine syndrome - Carcinoid syndrome - Gigantism - Short stature (Laron syndrome, Psychogenic dwarfism) - Multiple endocrine neoplasia (1, 2) - Progeria - Woodhouse-Sakati syndrome

External links
CRESCENTcme.org - The Critical RolE of Serum Calcium: An Educational Network for Secondary HyperparaThyroidism
Retrieved from "http://en.wikipedia.org/wiki/Secondary_hyperparathyroidism"
Categories: Parathyroid disorders

For information on another disease, click on Pancreatitis SOD Library

Articles: Hyperparathyroidism and Pancreatitis

The association of primary hyperparathyroidism and pancreatitis.
Prinz RA, Aranha GV.
The long-held tenet that a cause and effect relation exists between primary hyperparathyroidism and pancreatitis has recently been questioned. To clarify this association, records of 1475 patients seen with pancreatitis during a 10-year period were reviewed. Five patients (0.4%) were identified with primary hyperparathyroidism. The four men and one woman ranged in age from 31 to 57 years. Four had recurrent pancreatitis over a 2-10 yr period before hyperparathyroidism was diagnosed. One patient had hypercalcemia noted 1 year prior to developing pancreatitis. Four patients had associated potential causes of pancreatitis including alcohol abuse, gallstones, and hypotension. Pancreatitis was severe in each patient. Two patients had more than four admissions for acute pancreatitis, one patient underwent pseudocyst drainage and distal pancreatectomy for chronic pancreatitis, one patient underwent pancreaticojejunostomy for chronic pancreatitis, and one patient died from hemorrhagic pancreatitis. Four patients have undergone successful parathyroidectomy and have had no further attacks of pancreatitis on follow-up ranging from 1 to 4 years. Hyperparathyroidism is rarely associated with pancreatitis, but when this combination occurs, the pancreatitis is likely to be severe. Despite its rarity, a cause and effect relationship is still suggested by the fact that parathyroidectomy seems to prevent recurrence of pancreatitis.
PMID: 3994175 [PubMed - indexed for MEDLINE]

Hyperparathyroidism presenting as pancreatitis or complicated by postoperative pancreatitis.
Shepherd JJ.
Department of Surgery, University of Tasmania, Hobart, Australia.
BACKGROUND: The association of hyperparathyroidism with acute pancreatitis either pre-operatively or postoperatively has been questioned in recent overseas literature. METHODS: A review of medical records and histology reports in the Royal Hobart Hospital from 1971 to 1993 was carried out to identify all cases of acute pancreatitis associated with primary hyperparathyroidism. RESULTS: Seven cases are presented, six with histological confirmation, of hyperparathyroidism associated with pancreatitis in a period when 137 confirmed cases of primary hyperparathyroidism were treated. None of these patients had gallstones. In two, alcohol abuse may have been the aetiological factor. Five patients had successful neck exploration and none of them have experienced any further attacks including a 25 year old who had four hospitalizations and one laparotomy for pancreatitis in the year before parathyroidectomy 12 years ago. Two patients died from acute pancreatitis, one without exploration and the other with a mediastinal parathyroid adenoma that was not located at surgery. CONCLUSIONS: Most parathyroid surgeons would proceed to mediastinotomy, if necessary, at initial exploration in a patient with previous hypercalcaemic crisis. This should also be considered in patients with a history of acute pancreatitis.
PMID: 8602820 [PubMed - indexed for MEDLINE]

Hyperparathyroidism and chronic pancreatitis.
Smith MD, Pawlak M, Pantanowitz DP, Botha RJ.
Department of Surgery, University of the Witwatersrand, Johannesburg.
Hyperparathyroidism is a rare cause of pancreatitis. The nature of the relationship between the two entities is not well defined, i.e. is it casual or causal? We describe 2 patients with chronic pancreatitis and hyperparathyroidism who presented with epigastric pain and were initially treated unsuccessfully by surgical drainage of the pancreatic ducts. In 1 case the hyperparathyroidism was only recognised after the pancreatic surgery. In both the symptoms of chronic pancreatitis responded well to parathyroidectomy. We believe that our cases add support to a causal relationship between pancreatitis and hyperparathyroidism. Whatever the true relationship, management of these patients should initially be directed at the hyperparathyroidism, followed by appropriate treatment of the pancreatitis.
PMID: 10222803 [PubMed - indexed for MEDLINE]

[Acute pancreatitis associated with primary hyperparathyroidism]
[Article in Spanish]
Octavio de Toledo JM, Martín Eleno M, Mató JA, Alvarez C, Gómez Lorenzo F.
Servicio Galego de Saude, Xunta de Galicia, Hospital Nuestra Señora del Cristal, Orense.
A case of acute pancreatitis associated with primary hyperparathyroidism is reported. There was none of usual causes of pancreatitis, which did not recur following the removal of a parathyroid adenoma. There are over one hundred of cases of acute or chronic pancreatitis associated with hyperparathyroidism in the literature, suggesting a causal relationship between the two entities. The pancreatic disease has been attributed either to the hypercalcemia or to the excess of circulating parathyroid hormone. However, some authors have recently questioned any link between these two diseases.
PMID: 1751069 [PubMed - indexed for MEDLINE]

Acute relapsing pancreatitis in primary hyperparathyroidism with hypercalcemia aggravated after aspiration cytology: report of a case.
Chen CS, Tseng FY.
Department of Internal Medicine, Taipei Provincial Hospital, Taiwan R.O.C.
In 1957, Cope and his associates first noted 2 cases of pancreatitis associated with primary hyperparathyroidism. They emphasized the association of hyperparathyroidism and pancreatitis. Since then pancreatitis has become a diagnostic clue to primary hyperparathyroidism. We report herein a 39-year-old woman who had suffered from acute relapsing pancreatitis 3 times in the past 2 years. Hypercalcemia persisted throughout the course. A movable mass 3 x 3 cm in diameter was noted over the right thyroid area on physical examination. A hypoechogenic mass 3.5 x 2.7 x 1.4 cm was found between the right lobe of the thyroid and the carotid artery. Because of a persistently high serum level of Ca2+, normal saline and furosemide were infused; the serum Ca2+ decreased gradually. After aspiration of the suspected mass, the serum level of Ca2+ increased from 8.7 mg/dL to 18 mg/dL. Because of the impression of parathyroid adenoma, surgery was performed and a 3 x 2.5 x 1.5 cm well-encapsulated mass was excised without difficulty. Pathologic examination revealed a well-encapsulated parathyroid adenoma. This case reveals that primary hyperparathyroidism maybe one of the causes of pancreatitis, and aspiration cytology, although it may be helpful for the diagnosis, can aggravate the hypercalcemia.
PMID: 1686889 [PubMed - indexed for MEDLINE]