Hyposomatotropism (Growth Hormone Deficiency) Treatment & Management

Updated: Jan 24, 2019
  • Author: Sunil Kumar Sinha, MD; Chief Editor: Robert P Hoffman, MD  more...
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Treatment

Medical Care

Replacement dosages of recombinant human growth hormone (rhGH)

For patients with hyposomatotropism, effective replacement dosages of rhGH are 0.175-0.75 mg/kg/wk, and therapy should be individualized. Dividing the weekly dose into 6 or 7 daily subcutaneous injections is more effective than dividing the total dose into 3 doses administered on alternate days. [66, 67]

Height outcome

In the authors' personal experience in treating patients with GH deficiency (GHD) starting at younger than 4 years, the patient's final height may exceed the target height.

The patient's final height is best correlated with his or her pretreatment chronologic age. It is also related to the height standard deviation score and to the child's predicted adult height, duration of therapy, and birth length. In many studies, the final height was closely correlated with the height standard deviation score, the patient's age at onset of puberty, weight, and serum concentrations of GH binding protein (indicators of GH receptor mass).

Early recognition of GHD is essential for an optimal outcome in terms of height.

Patterns of growth during childhood

Growth during childhood follows predictable patterns:

  • Before birth - Prenatal growth averages 1.2-1.5 cm each week.

  • Infancy and childhood - Growth velocity increases to 15 cm (approximately 6 inches) per year over the first 2 years and then slows to 6 cm (approximately 2 inches) per year until puberty.

  • Puberty - A second peak in growth velocity occurs during puberty. This peak occurs earlier but is lower in magnitude and is shorter in girls than in boys.

The table below summarizes the pubertal peak of growth velocity in children.

Table. Characteristics of the Pubertal Peak of Growth Velocity in Girls and Boys (Open Table in a new window)

Characteristic

Girls

Boys

Mean age at peak height velocity, y

11.5

13

Magnitude, cm/y

8.5

9.5

Duration, y

5

6

In children who are receiving rhGH therapy, growth velocity usually exceeds reference values in the first few years. Therefore, suspect partial GH resistance or noncompliance if suboptimal growth velocity is observed at the beginning of rhGH therapy.

Treatment principles

Management includes the following:

  • Monitor patients with visits every 3 months.
  • Conduct physical examination: Perform funduscopy to exclude pseudotumor cerebri. Pubertal staging should be performed during each visit because gonadal steroids have a notable effect on skeletal maturation. Monitor patients by measuring their height in centimeters and weight in kilograms.
  • Obtain interim histories. Monitor medical therapy. Adjust drug dosages by weight, and monitor patients for adverse effects of therapy (see Medication).
  • For patients whose condition does not respond well to weight-based therapy, some clinicians advocate titrating dosages according to insulinlike growth factor (IGF)-1 levels. The goal is to maintain an IGF-1 value in the upper quartile for the child's age and sex.
  • Bone age can be used to determine the remaining growth potential for patients with GHD who are approaching their final height. Bone ages have no proven role in monitoring GH therapy.
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Consultations

Consultations with the specialists listed below may aid in the care of patients with hyposomatotropism.

  • Neurosurgeon

  • Plastic surgeon

  • Radiation oncologist

  • Neurooncologist

  • Psychologist

  • Nutritionist

Brain tumors and/or secondary hydrocephalus indicate a need for consultation with a neurosurgeon.

A pediatric surgeon may be consulted to address cleft lip repair, cleft palate repair, and/or cosmetic reconstruction of the facies in a patient with long-standing GHD.

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Complications

Recombinant human growth hormone (rhGH), which is used to treat hyposomatotropism, has a well-established profile of adverse effects in the pediatric population. rhGH reduces insulin sensitivity, resulting in hyperglycemia among patients who are predisposed to develop insulin resistance. [68]

Slipped capital femoral epiphysis occurs more frequently in patients with renal or endocrine disorders or in patients undergoing rapid growth than in the general population.

Scoliosis may progress in patients with rapid growth secondary to rhGH therapy. [69]

Intracranial hypertension with papilledema, visual changes, headaches, nausea, and/or vomiting have been reported in a small number of patients treated with rhGH. The symptoms usually occurred within the first 8 weeks of initiating rhGH therapy.

Funduscopic examination is recommended at start of rhGH therapy and at each follow-up visit.

Peripheral edema and prepubertal gynecomastia have been associated with rhGH therapy. [70]

With the exception of slipped capital femoral epiphysis, most adverse effects associated with rhGH therapy resolve after the dosage is reduced or after therapy ends.

Potential need to discontinue rhGH therapy

Therapy with rhGH may need to be discontinued in patients who have acute critical conditions or illnesses, such as open heart or abdominal surgery, multiple accidental trauma, or respiratory failure. The safety of continuing rhGH treatment has not been established in patients receiving replacement doses for approved indications who concurrently develop these critical illnesses.

In a study of adults without GHD who were hospitalized for critical illness, supplemental rhGH therapy may have been associated with a significant increase in mortality rates. Jeschke et al performed a prospective, randomized, placebo-controlled study in pediatric patients hospitalized for severe burns. [71]  The mortality risk did not increase with rhGH therapy.

Potential association between rhGH therapy and increased cancer risk

GH raises serum concentrations of IGF-1 (insulin-like growth factor-1), which is mitogenic and antiapoptotic in vitro, and adult levels of which have been associated in most studies with risks of subsequent breast, colorectal and prostate cancers, and in some studies with other cancers.

Watanabe and colleagues reported an increased frequency of leukemia in Japanese children who were treated with rhGH. [72]  Several investigators subsequently examined the potential relationship between rhGH therapy and leukemia. Children with GHD have more risk factors that predispose them to develop leukemia than do children in the general population. These factors include the following:

  • Previous episodes of cancer

  • Treatment with modalities such as irradiation and chemotherapy

  • Comorbid conditions, such as, Down syndrome, Bloom syndrome, or Fanconi syndrome

Examination of large databases reveals that the incidence of leukemia is not elevated among rhGH-treated patients without these additional risk factors. In addition, no current evidence suggests that the risk of leukemia or brain-tumor recurrence rises in patients receiving long-term rhGH treatment. [72, 73]

A large cross-European cohort, the SAGhE (Safety and Appropriateness of Growth Hormone Treatments in Europe) study of nearly 24,000 patients treated with rhGH reported results that did not support a carcinogenic effect of rhGH; however, the researchers noted that the unexplained trend in cancer mortality risk in relation to GH dose in patients with previous cancer, and the indication of possible effects on bone cancer, bladder cancer and Hodgkin lymphoma risks, need further investigation. [74]

Patients with cancer in remission who require rhGH should be evaluated carefully. The pediatric endocrinologist and the oncologist should assess the appropriateness of rhGH therapy on an individual basis.

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