Secondary

hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparathyroidism) or as response to external stimuli (secondary hyperparathyroidism). ...

is the medical condition of excessive secretion of

parathyroid hormone Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine. PTH influences bone re ...

(PTH) by the

parathyroid gland Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes pa ...

s in response to

hypocalcemia Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L) while levels less than 2.1 mmol ...

(low

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...

levels), with resultant

hyperplasia Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferati ...

of these glands. This disorder is primarily seen in patients with chronic kidney failure. It is sometimes abbreviated "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 the blood, immune system, and neurological system.

Cause

Chronic kidney failure Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vom ...

is the most common cause of secondary hyperparathyroidism. Failing

kidneys The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

do not convert enough

vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...

to its active form, and they do not adequately excrete

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...

. When this happens, insoluble

calcium phosphate The term calcium phosphate refers to a family of materials and minerals containing calcium ions (Ca2+) together with inorganic phosphate anions. Some so-called calcium phosphates contain oxide and hydroxide as well. Calcium phosphates are white ...

forms in the body and removes calcium from the circulation. Both processes lead to hypocalcemia and hence secondary hyperparathyroidism. Secondary hyperparathyroidism can also result from malabsorption (

chronic pancreatitis Chronic pancreatitis is a long-standing inflammation of the pancreas that alters the organ's normal structure and functions. It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pa ...

, small bowel disease, malabsorption-dependent

bariatric surgery Bariatric surgery (or weight loss surgery) includes a variety of procedures performed on people who are obese. Long term weight loss through the standard of care procedures ( Roux en-Y bypass, sleeve gastrectomy, and biliopancreatic diversion ...

) 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. A few other causes can stem from inadequate dietary intake of calcium, a vitamin D deficiency, or

steatorrhea Steatorrhea (or steatorrhoea) is the presence of excess fat in feces. Stools may be bulky and difficult to flush, have a pale and oily appearance, and can be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may oc ...

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 kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

or defective calcium receptors on the surface of parathyroid glands.

Treatment

If the underlying cause of the hypocalcemia can be addressed, the hyperparathyroidism will resolve. In people with chronic

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

, treatment consists of dietary restriction of phosphorus; supplements containing an active form of

, such as

calcitriol Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the ...

doxercalciferol Doxercalciferol (or 1-hydroxyergocalciferol, trade name Hectorol) is drug for secondary hyperparathyroidism and metabolic bone disease. It is a synthetic analog of ergocalciferol (vitamin D2). It suppresses parathyroid synthesis and secretion. ...

paricalcitol Paricalcitol (chemically it is 19-nor-1,25-(OH)2-vitamin D2. Marketed by Abbott Laboratories under the trade name Zemplar) is a drug used for the prevention and treatment of secondary hyperparathyroidism (excessive secretion of parathyroid horm ...

; and

phosphate binders Phosphate binders are medications used to reduce the absorption of dietary phosphate; they are taken along with meals and snacks. They are frequently used in people with chronic kidney failure (CKF), who are less able to excrete phosphate, resulting ...

, which are either calcium-based and non-calcium based. Extended Release Calcifediol was recently approved by the FDA as a treatment for secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic kidney disease (CKD) and low vitamin D blood levels (25-hydroxyvitamin D less than 30 ng/mL). It can help treat SHPT by increasing Vitamin D levels and lowering parathyroid hormone or PTH. It is not indicated for people with stage 5 CKD or on dialysis. In the treatment of secondary hyperparathyroidism due to chronic kidney disease on dialysis

calcimimetic A calcimimetic is a pharmaceutical drug that mimics the action of calcium on tissues, by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues. Calcimimetics are used to treat secondary hyperparathyro ...

s do not appear to affect the risk of early death. It does decrease the need for a

parathyroidectomy Parathyroidectomy is the surgical removal of one or more of the (usually) four parathyroid glands. This procedure is used to remove an adenoma or hyperplasia of these glands when they are producing excessive parathyroid hormone (PTH): hyperparathy ...

but caused more issues with low blood calcium levels and

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

. Most people with hyperparathyroidism secondary to chronic kidney disease will improve after renal transplantation, but many will continue to have a degree of residual hyperparathyroidism (tertiary hyperparathyroidism) post-transplant with associated risk of bone loss, etc.

Prognosis

If left untreated, the disease will progress to

tertiary hyperparathyroidism Tertiary hyperparathyroidism is a condition involving the overproduction of the hormone, parathyroid hormone, produced by the parathyroid glands. The parathyroid glands are involved in monitoring and regulating blood calcium levels and respond by ...

, where correction of the underlying cause will not stop excess PTH secretion, i.e. parathyroid gland hypertrophy becomes irreversible. In contrast with secondary hyperparathyroidism, tertiary hyperparathyroidism is associated with hypercalcemia rather than hypocalcemia.

References

External links

{{Parathyroid disease Parathyroid disorders