Hyperparathyroidism - Paediatrics - Lecture Slides, Slides of Pediatrics

Download Hyperparathyroidism - Paediatrics - Lecture Slides and more Slides Pediatrics in PDF only on Docsity!

Hyperparathyroidism

Parathyroid Hormone (PTH)

• Is an 84 aminoacid chain, but its biologically activity resides in

the first 34 residues.

• In the parathyroid gland, a Pre-Pro-PTH are synthesized
• Pre-Pro-PTH is converted to Pro-PTH and Pro-PTH converted

to PTH.

• When serum Calcium level falls, signal is transduced through

calcium sensing receptors, and secretion of PTH increased.

Parathyroid Hormone (PTH)

• The calcium sensing receptor:

• Gain of function mutations result in depressed secretion of PTH in response to hypocalcemia, leading to syndrome of Familial Hypocalcemia with Hypercalciuria

Parathyroid Hormone related peptide

(PTHrP)

• Is homologous to PTH only in the first 13 aa of its amino

terminus, 8 of which are identical to PTH.

• Its gene is on the short arm of chromosome 12 and that of

PTH is on the short arm of chromosome 11.

• PTHrP, like PTH, activates PTH receptors in kidney and bone

cells.

• It is produced in almost every type of cells in the body,

including every tissue of the embryo at certain stage of development.

Definition

• Hyperparathyroidism describes proliferation of the parathyroid hormone (PTH)–secreting cells, or chief cells, in one or more of the 4 parathyroid glands.
• The cause may be due to a genetic mutation, as in primary hyperparathyroidism, or to a variety of underlying conditions that produce secondary hyperparathyroidism due to hypocalcemia, such as intestinal malabsorption, or high serum phosphorus levels, such as with chronic renal failure.

Definition

• Tertiary hyperparathyroidism usually exists in situations of

secondary hyperparathyroidism. Tertiary hyperparathyroidism occurs when parathyroid hyperplasia becomes so severe that removal of the underlying cause does not eliminate the stimulus for PTH secretion and hypertrophic chief cells become autonomous.

Pathophysiology

• This reduction is associated with an increased amount of

circulating calcium, which is required to suppress PTH secretion.

• The reduction may be caused by genetic mutation (eg, familial

hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism), multiple endocrine neoplasia (MEN), or conditions that would normally stimulate compensatory PTH secretion

Pathophysiology

• Conditions include calcium or vitamin D malabsorption, accumulation of phosphate with inability to excrete it (eg, chronic renal failure), and uremia.
• In addition, some genetic mutations have been described in primary hyperparathyroidism, including relocation of the PTH gene to a site next to an oncogene.
• Loss of one copy of a tumor suppressor gene on chromosome 11 has also been reported in some patients with multiple endocrine neoplasia type 1 (MEN I) syndrome

Mortality/Morbidity

 The morbidity from primary hyperparathyroidism is most often due to hypercalcemia.

 This can take the form of bradycardia and heart block and dehydration due to polyuria, nausea, vomiting, and poor fluid intake. Pancreatitis has also been reported.

 Other causes of morbidity observed with primary hyperparathyroidism may be due to effects of associated tumors, such as jaw tumors or Wilms tumor.

 Morbidity from secondary hyperparathyroidism usually involves demineralization of bones with subsequent pain, fracturing, or deformity.

History

• Primary hyperparathyroidism

o Most commonly, patients present without symptoms. Hyperparathyroidism may be diagnosed in an otherwise asymptomatic patient by incidental discovery during routine blood chemistry analysis of hypercalcemia. o Symptoms of early disease, when present, are specific to hypercalcemia.

• They include muscle weakness, depression, increased sleepiness, nausea, vomiting, acute abdominal pain (which might be the result of pancreatitis), constipation, and polydipsia.
• Frequent and occasionally painful urination and dysuria and/or back pain may be observed, the latter from nephrolithiasis.

Physical Exam.

• Primary hyperparathyroidism

o Signs of dehydration due to hypercalcemia, such as tenting of skin, prolonged capillary refill time, and dry mucous membranes.

o Bradycrardia. With or without irregular heartbeat.

o Decreased muscle tone and somnolence.

Physical Exam.

• Secondary hyperparathyroidism

• Skeletal deformity
• Decreased muscle tone
• Bone pain on palpation
• Short stature

Eitiology

3. Iatrogenic causes: 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. The mechanism for this is not presently clear.
4. Cholestatic liver disease: Contrary to previous belief, not all children with chronic cholestatic liver disease have secondary hyperparathyroidism. Many of these patients, as well as adults with chronic liver disease, have levels of PTH within the reference range.

Eitiology

 Neonatal severe hyperparathyroidism: symptoms

develop shortly after birth and consist of anorexia,

irritability, lethargy, constipation, and failure to thrive.

• Radiograph reveal subperiosteal bone resorption, osteoparosis, and pathological fractures.
• Symptoms maybe mild, resolving without treatment or may have rapidly fatal course if diagnosis and treatment are delayed.