This page is presented for educational purposes and is not meant to describe Novo Nordisk products.

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Pediatric GHD
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Noonan Syndrome
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Turner Syndrome
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Children Born Small for Gestational Age (SGA)
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overview of Turner syndrome

Turner syndrome is a chromosomal condition caused by a complete or partial absence of the second sex chromosome.¹ It affects females only, at a rate of approximately one out of every 2500 female live births.¹ Short stature is probably the most common, readily recognizable clinical feature of Turner syndrome; on average, untreated patients attain an adult height that is 20 cm shorter than target height.¹ Additional clinical features of Turner syndrome include characteristic facial features, cardiovascular system problems, genitourinary system problems,^1,2 and additional manifestations. There is a high prevalence of otitis media that may result from an abnormal relationship between the Eustachian tube and middle ear, a consequence of abnormal cranial base anatomy. As a result of otitis media, conductive hearing loss is common in young girls with Turner syndrome.¹

^* Untreated patients

Diagnosis of Turner syndrome

A diagnosis of Turner syndrome may be considered when there are a number of characteristic physical features observed, such as ptosis, epicanthal folds, hypertelorism, retrognathic face, and micrognathia.² Many patients with Turner syndrome also exhibit cardiovascular system problems, including aortic coarctation, bicuspid aortic valve, conduction abnormalities, and hypertension.¹ Genitourinary system problems include gonadal failure and congenital renal malformation.^1,2

Short stature is probably the most common, readily recognizable clinical feature of Turner syndrome; on average, untreated patients attain an adult height that is 20 cm shorter than target height.¹

Many girls are diagnosed in early childhood when short stature and other features are identified. Diagnosis sometimes takes place later in cases where puberty does not occur.

Diagnosis is confirmed by a blood test, called a karyotype. This test is used to analyze the chromosomal composition of the female and confirm the complete or partial absence of the second sex chromosome.¹

References

Bondy CA; Turner Syndrome Consensus Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007;92(1):10-25.
Lippe BM, Saenger PH. Turner syndrome. In: Sperling MA. Pediatric Endocrinology. 2nd ed. Philadelphia, PA: Saunders; 2002:519-564.

Indications and Usage:

Norditropin^® (somatropin [rDNA origin] injection) is indicated for the treatment of children with growth failure due to inadequate secretion of endogenous growth hormone, the treatment of children with short stature associated with Noonan syndrome or Turner syndrome, the treatment of children with short stature born small for gestational age (SGA) with no catch-up growth by age 2-4 years, and for the replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD) who meet either of the following two criteria: 1. Adult Onset: Patients who have GHD, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or 2. Childhood Onset: Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.

Important Safety Information:

Somatropin should not be used to treat patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure as increased mortality may occur.

Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Norditropin^® is not indicated for the treatment of patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

Somatropin should not be used or should be discontinued with any evidence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Patients with preexisting tumors or GHD secondary to an intracranial lesion should be monitored routinely for progression or recurrence. In childhood cancer survivors, an increased risk of a second neoplasm, particularly meningiomas in patients treated with radiation to the head for their first neoplasm, has been reported in patients treated with somatropin.

Somatropin should not be used in patients with active proliferative or severe non-proliferative diabetic retinopathy, for growth promotion in pediatric patients with closed epiphyses, or in patients with known hypersensitivity to somatropin or any of its excipients.

Somatropin may decrease insulin sensitivity particularly at higher doses in susceptible patients. Glucose levels should be monitored periodically, including close monitoring of patients with preexisting diabetes or glucose intolerance. Doses of anti-hyperglycemic drugs (insulin or oral agents) may require adjustment for patients with diabetes on somatropin therapy.

Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting, usually occurring within the first eight (8) weeks after initiation of somatropin therapy, has been reported in a small number of patients. In all reported cases, rapid resolution has occurred after therapy cessation or a reduction of dose.

Funduscopic examination should be performed routinely before and during somatropin therapy. If papilledema is observed, somatropin treatment should be discontinued.

Fluid retention during somatropin replacement therapy in adults may frequently occur. Clinical manifestations of fluid retention are usually transient and dose dependent.

In patients with GHD, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Periodic thyroid function tests are recommended and thyroid hormone replacement therapy should be initiated or adjusted as needed.

Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders (including GHD and Turner syndrome) or with rapid growth. Onset of a limp or complaints of hip or knee pain in somatropin patients should be carefully evaluated. Rapid growth may also result in progression of preexisting scoliosis. Patients with a history of scoliosis or skeletal abnormalities, which may be present in untreated Noonan, Turner or Prader-Willi syndrome, should be monitored.

Patients with Turner Syndrome should be evaluated carefully for otitis media and other ear disorders since these patients have an increased risk of ear and hearing disorders. Somatropin treatment may increase the occurrence of otitis media in patients with Turner syndrome. Somatropin may also increase the risk of IH in Turner patients. In addition, patients with Turner syndrome should be monitored closely for cardiovascular disorders (e.g., stroke, aortic aneurysm/dissection, hypertension) as these patients are also at risk for these conditions.

Congenital heart disease is an inherent component of Noonan syndrome. Though a clinical study in Noonan syndrome reported no evidence of somatropin-induced ventricular hypertrophy or exacerbation of preexisting ventricular hypertrophy (as judged by echocardiography), the safety of Norditropin^® in children with Noonan syndrome and significant cardiac disease is not known.

Other somatropin-related adverse reactions include injection site reactions/rashes, lipoatrophy and headaches. Subcutaneous injection of somatropin at the same site repeatedly may result in tissue atrophy and can be avoided by rotating the injection site.

Somatropin inhibits 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD-1) in adipose/hepatic tissue, and may significantly impact the metabolism of cortisol and cortisone. In patients treated with somatropin, previously undiagnosed central (secondary) hypoadrenalism may be unmasked requiring glucocorticoid replacement therapy. In addition, patients treated with glucocorticoid replacement therapy, especially with cortisone acetate and prednisone, for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses.

Careful monitoring is advisable when somatropin is administered in combination with other drugs known to be metabolized by CP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, cyclosporine) as limited published data suggest somatropin may alter clearance of these compounds.

In adult women on oral estrogen replacement, a larger dose of somatropin may be required to achieve the defined treatment goal.

The safety and effectiveness of Norditropin^® in patients age 65 years and older has not been evaluated in clinical studies. Elderly patients may be more sensitive to the actions of somatropin and may be more prone to develop adverse reactions.