Objectives

Importance of Ca in body:
Bone mineralization. Blood coagulation. Neuromuscular transmission. Neurotransmitter release. Contraction of all muscle types. Cell membrane permeability and excitability. Secretion of glands.

Control Of Ca Homeostasis
1- PTH:
raises plasma Ca level if it is lowered by: -Vit. D activation Ca absorption. - Ca reabsorption in DCT. - PO4 reabsorption in PCT. - Ca mobilization from bone.

2- CALCITONIN:
lowers plasma Ca level if it is raised by: - Ca absorption. - PO4 reabsorption in PCT. - Ca mobilization from bone. 3- VITAMIN D: - Ca absorption. - Ca bone uptake and deposition.

Definition

Hyperparathyroidism is an endocrine disorder caused by excessive secretion of parathyroid hormone (PTH) from the parathyroid glands.

Statistics

Incidence
28 per 100,000 Americans can be expected to develop

hyperparathyroidism per year.

Prevalence
Primary hyperparathyroidism in adults: 1/500-1000

population. Its true prevalence in children is unknown, but it is considered rare Prevalence of secondary and tertiary hyperparathyroidism depends on prevalence of the underlying disease Postmenopausal women have the highest incidence of primary hyperparathyroidism and fractures Prevalence increases with age, but hyperparathyroidism can affect people of all ages, including children

Statistics
Gender Primary hyperparathyroidism

3:1 female to male ratio, varying from close

to unity in people younger than 40 years to 5:1 in those older than 75 years

Postmenopausal women In women aged 60 years and older

2/1000 will get hyperparathyroidism

Primary

Common disease that occurs when one or more of the parathyroid glands becomes overactive. Patients with primary disease are almost always hypercalcemic In 85% of patients with primary hyperparathyroidism, hypercalcemia is due to a parathyroid adenoma. Loss of sensitivity of these proliferating chief cells to normal extracellular calcium concentrations occurs Hypercalcemia is usually discovered during a routine serum chemistry profile

Secondary
Occurs in patients with kidney failure or severe vitamin D deficiency. The vast majority of cases demonstrate only chief cell hyperplasia Patients are almost always normocalcemic Approximately 20% of patients with hyperparathyroidism have renal calculi

Etiology

Common causes
Primary hyperparathyroidism: most cases (85%) - single parathyroid gland malfunctioning and developing into an adenoma. 15% of cases, multiple adenomas or hyperplasia Ectopic parathyroid glands Secondary hyperparathyroidism: vitamin D deficiency chronic kidney disease

Etiology

Rare causes Primary hyperparathyroidism

Radiation therapy to the head and neck area for

benign diseases during childhood Multiple endocrine neoplasia (MEN-1, MEN-2)

Secondary hyperparathyroidism
Pseudohypoparathyroidism due to parathyroid

hormonereceptor G protein mutation Less common conditions associated with vitamin D deficiency or resistance include
malabsorption cholestatic liver or biliary disease drugs (eg, anticonvulsants, rifampin, ketoconazole, 5-

FU/leucovorin)

Etiology

Serious causes Primary hyperparathyroidism:

Parathyroid cancer

Secondary hyperparathyroidism:
Chronic kidney disease or end-stage renal disease

(ESRD) Vitamin D deficiency Metastatic prostate cancer Iatrogenic causes such as lithium administration: may decrease the ability of circulating levels of calcium that are within the reference range to suppress PTH secretion (mechanism unclear)

Symptoms
Disease of bones, stones, abdominal groans and psychic moans" Skeletal manifestations
Bone and joint pain esp. in hand and feet (pseudogout).

Renal

manifestations

polyuria, dysuria, renal colic or stone passage.

Gastrointestinal
peptic symptoms.

manifestations

anorexia, nausea, vomiting, abdominal pain, constipation,

Symptoms
Neuromusculopsychologic

manifestations
proximal muscle weakness, easy fatigability, depression,

inability to concentrate, and memory problems that are often poorly characterized and may not be noted by the patient.

Cardiovascular

manifestations

palpitation and hypertensive symptoms.

Asymptomatic hypercalcemia in most cases.

Signs and symptoms

Signs
Primary hyperparathyroidism: Signs of dehydration due to hypercalcemia Bradycardia, with or without irregular heartbeat Decreased muscle tone and somnolence Gastric and/or duodenal ulcer Secondary hyperparathyroidism: Skeletal deformity Decreased muscle tone Bone pain on palpation Short stature

Signs and symptoms

Symptoms
Primary hyperparathyroidism: Symptoms of early disease, when present, are specific to hypercalcemia Muscle weakness Psychiatric symptoms, including depression, dementia, confusion, and stupor Increased sleepiness Nausea, vomiting Acute abdominal pain (which might be the result of pancreatitis), constipation Polyuria, polydipsia Frequent and occasionally painful urination and dysuria Back pain (from kidney stones) Heartburn or associated pain from acid reflux

Signs and symptoms

Secondary hyperparathyroidism: History of underlying disease such as renal or intestinal conditions Musculoskeletal symptoms: bone pain, muscle weakness, previous fracture

Diagnosis
Serum calcium Intact PTH Serum phosphorus Urine calcium 25-hydroxyvitamin D Bone densitometry Radiography Technetium-99m-sestamibi scanning

Treatment

Parathyroidectomy and MIRP surgery Bisphosphonates Raloxifene Cinacalcet

(secondary hyperparathyroidism due to CKD)

Calcitriol
(secondary hyperparathyroidism due to CKD)

Ergocalciferol
(secondary hyperparathyroidism due to CKD)

Paricalcitol
(secondary hyperparathyroidism due to CKD)

Lifestyle adjustments