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Growth Hormone deficiency

Updated : February 16, 2024





Background

The growth hormone (GH) deficiency is a condition resulting from limited or lack of growth hormone production; in adults, it is characterized by short stature, decreased bone and muscle mass, decreased bone mineral density, change in the body fat composition and distribution with increased central obesity, hyperlipidemia and deposition and formation of fatty deposits in the arteries (atherogenesis).

It is generally accompanied by a change in mood and general well-being. Therapy usually aims at the replacement of the deficiency with the growth hormone.

Epidemiology

An estimated prevalence of adult life GH deficiency persisted from childhood is about 3: 10,000 people. According to the Danish nationwide study of GH deficiency registries, the incidence rate of childhood onset in males was about 2.5% and 1.70% in females per 1,00,000 individuals. The incidence of adult-onset in males was reported to be 1.90 % and in females with 1.42% per 1,00,000 individuals.

The incidence rate is higher in males than females in individuals with age 45 years and above, while no age-specific difference is observed in the age group of individuals with a range of 18-44 years. An increase in idiopathic cases is observed from 13.9% to 19.3% in the nationwide registries.

Anatomy

Pathophysiology

The anterior pituitary gland produces growth hormones. As an adult matures, with the increase in age, GH’s secretion from the anterior pituitary diminishes. The hormone-insulin-like growth factor 1 (IGF-1), primarily synthesized by the liver, is stimulated.

These hormones together are responsible for growth in children and maintenance of bone and muscle mass in adulthood, its role in maintaining the psychological well-being in adults remains poorly understood. Adult-onset GH deficiency is often acquired from hypopituitarism, pituitary tumor, cranial irradiation, trauma to the brain, and idiopathic.

Most cases which arise in adulthood are generally undetected in childhood. GH deficiency has been associated with metabolic, skeletal, cardiovascular, and neuro-psychiatric cognitive impairments. Most of these abnormalities are reversed after growth hormone therapy.

Etiology

The congenital cause of growth hormone deficiency is considered a genetic error. It is usually associated with defects in the brain structure or midline facial defects such as cleft palate or single central incisor. GH deficiency is characterized by growth retardation in utero. The risk of passing the gene to the offspring is about 50%.

Male and female children possess the same risk. Consanguineous marriage has a higher chance than unrelated parents of carrying the abnormal gene, increasing the risk of offspring with a recessive, dominant genetic disorder. Female carriers with X-linked disorder have a 25% chance of passing the gene with each pregnancy.

Genetics

Female carriers with each pregnancy have a chance of about 25-50% of passing the gene. Consanguineous marriage has higher chances of gene mutations. A genetic factor is considered chiefly in the cases of childhood onset of the disease.

Prognostic Factors

According to the research evidence observed over two decades, individuals with adult-onset growth hormone deficiency have higher premature mortality.

Factors associated with mortality are bone mineralization, increased risk of bone fractures, higher levels of LDL, Cholesterol, pituitary tumors, poor thermoregulation, decrease insulin sensitivity, neuropsychiatry and cardiovascular abnormalities, and poor quality of life.

Depression is often associated with stature, social isolation, affected mood levels, and fatigue.

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

 

macimorelin 

0.5 mg/kg orally after an 8-hour fast
Recommendations before use:
Prior to administering macimorelin, a sufficient washout time of drugs known to prolong the QT interval is recommended.
Discontinue strong CYP3A4 inducers and GH therapy.



somatrem 

4 units three times a week. can be given as subcutaneous or Intramuscular injection



sermorelin 

Indicated for diagnosis of GH deficiency
1 mcg/kg intravenously each day after fasting overnight
It can be used in combination with different diagnostic tests



somatotropin 

(Non-weight based)
Start with Norditropin 0.2 mg daily; the recommended range is 0.15 mg- 0.3 mg daily & escalate the daily dose at intervals of 1 to 2 months, with an increase of around 0.1 mg -0.2 mg daily
Based on requirements of every individual, considering their clinical response and levels of serum IGF-1
(Weight-based)
Start with Norditropin 0.004 mg/kg in a day to address individual patient needs, escalate the dosage incrementally up to a maximum of 0.016 mg/kg in a day



somatorelin 

1µg/kg IV in the morning, followed by a fasting night
Dose for standard body weight: 50µg
It is also indicated to study aging, sleep disorders, and cognitive impairment



 

somatropin 

Genotropin
0.16-0.24 mg/kg per week; divided into equal 6-7 subcutaneously (SC) doses/week
Humatrope
0.18-0.3 mg/kg/week subcutaneously (SC); divided into equal 6-7 subcutaneously (SC) doses/week
Norditropin
0.17-0.24 mg/kg/week subcutaneously (SC); divided into equal 6-7 subcutaneously (SC) doses/week
Nutropin and Nutropin AQ
0.3 mg/kg/week subcutaneously (SC) weekly divided into equal daily doses
Omnitrope
0.16-0.24 mg/kg/week subcutaneously (SC) divided into 6-7 doses/week
Saizen
0.18 mg/kg/week subcutaneously (SC) /IM divided into equal doses
Zomacton
Up to 0.1 mg/kg subcutaneously (SC) 3 times/week



somatrogon-ghla 


Indicated for Growth Hormone Deficiency
Age >3 years
0.66 mg/kg of body weight subcutaneously every week
Adjust the dosage for each patient according to their growth response



sermorelin 

30 mcg/kg subcutaneously each day at bedtime



somatotropin 

Take 0.17 mg/kg-0.24 mg/kg given in a week i.e 0.024 mg/kg -0.034 mg/kg daily



 

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK425701/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386113/#

Growth Hormone deficiency

Updated : February 16, 2024




The growth hormone (GH) deficiency is a condition resulting from limited or lack of growth hormone production; in adults, it is characterized by short stature, decreased bone and muscle mass, decreased bone mineral density, change in the body fat composition and distribution with increased central obesity, hyperlipidemia and deposition and formation of fatty deposits in the arteries (atherogenesis).

It is generally accompanied by a change in mood and general well-being. Therapy usually aims at the replacement of the deficiency with the growth hormone.

An estimated prevalence of adult life GH deficiency persisted from childhood is about 3: 10,000 people. According to the Danish nationwide study of GH deficiency registries, the incidence rate of childhood onset in males was about 2.5% and 1.70% in females per 1,00,000 individuals. The incidence of adult-onset in males was reported to be 1.90 % and in females with 1.42% per 1,00,000 individuals.

The incidence rate is higher in males than females in individuals with age 45 years and above, while no age-specific difference is observed in the age group of individuals with a range of 18-44 years. An increase in idiopathic cases is observed from 13.9% to 19.3% in the nationwide registries.

The anterior pituitary gland produces growth hormones. As an adult matures, with the increase in age, GH’s secretion from the anterior pituitary diminishes. The hormone-insulin-like growth factor 1 (IGF-1), primarily synthesized by the liver, is stimulated.

These hormones together are responsible for growth in children and maintenance of bone and muscle mass in adulthood, its role in maintaining the psychological well-being in adults remains poorly understood. Adult-onset GH deficiency is often acquired from hypopituitarism, pituitary tumor, cranial irradiation, trauma to the brain, and idiopathic.

Most cases which arise in adulthood are generally undetected in childhood. GH deficiency has been associated with metabolic, skeletal, cardiovascular, and neuro-psychiatric cognitive impairments. Most of these abnormalities are reversed after growth hormone therapy.

The congenital cause of growth hormone deficiency is considered a genetic error. It is usually associated with defects in the brain structure or midline facial defects such as cleft palate or single central incisor. GH deficiency is characterized by growth retardation in utero. The risk of passing the gene to the offspring is about 50%.

Male and female children possess the same risk. Consanguineous marriage has a higher chance than unrelated parents of carrying the abnormal gene, increasing the risk of offspring with a recessive, dominant genetic disorder. Female carriers with X-linked disorder have a 25% chance of passing the gene with each pregnancy.

Female carriers with each pregnancy have a chance of about 25-50% of passing the gene. Consanguineous marriage has higher chances of gene mutations. A genetic factor is considered chiefly in the cases of childhood onset of the disease.

According to the research evidence observed over two decades, individuals with adult-onset growth hormone deficiency have higher premature mortality.

Factors associated with mortality are bone mineralization, increased risk of bone fractures, higher levels of LDL, Cholesterol, pituitary tumors, poor thermoregulation, decrease insulin sensitivity, neuropsychiatry and cardiovascular abnormalities, and poor quality of life.

Depression is often associated with stature, social isolation, affected mood levels, and fatigue.

macimorelin 

0.5 mg/kg orally after an 8-hour fast
Recommendations before use:
Prior to administering macimorelin, a sufficient washout time of drugs known to prolong the QT interval is recommended.
Discontinue strong CYP3A4 inducers and GH therapy.



somatrem 

4 units three times a week. can be given as subcutaneous or Intramuscular injection



sermorelin 

Indicated for diagnosis of GH deficiency
1 mcg/kg intravenously each day after fasting overnight
It can be used in combination with different diagnostic tests



somatotropin 

(Non-weight based)
Start with Norditropin 0.2 mg daily; the recommended range is 0.15 mg- 0.3 mg daily & escalate the daily dose at intervals of 1 to 2 months, with an increase of around 0.1 mg -0.2 mg daily
Based on requirements of every individual, considering their clinical response and levels of serum IGF-1
(Weight-based)
Start with Norditropin 0.004 mg/kg in a day to address individual patient needs, escalate the dosage incrementally up to a maximum of 0.016 mg/kg in a day



somatorelin 

1µg/kg IV in the morning, followed by a fasting night
Dose for standard body weight: 50µg
It is also indicated to study aging, sleep disorders, and cognitive impairment



somatropin 

Genotropin
0.16-0.24 mg/kg per week; divided into equal 6-7 subcutaneously (SC) doses/week
Humatrope
0.18-0.3 mg/kg/week subcutaneously (SC); divided into equal 6-7 subcutaneously (SC) doses/week
Norditropin
0.17-0.24 mg/kg/week subcutaneously (SC); divided into equal 6-7 subcutaneously (SC) doses/week
Nutropin and Nutropin AQ
0.3 mg/kg/week subcutaneously (SC) weekly divided into equal daily doses
Omnitrope
0.16-0.24 mg/kg/week subcutaneously (SC) divided into 6-7 doses/week
Saizen
0.18 mg/kg/week subcutaneously (SC) /IM divided into equal doses
Zomacton
Up to 0.1 mg/kg subcutaneously (SC) 3 times/week



somatrogon-ghla 


Indicated for Growth Hormone Deficiency
Age >3 years
0.66 mg/kg of body weight subcutaneously every week
Adjust the dosage for each patient according to their growth response



sermorelin 

30 mcg/kg subcutaneously each day at bedtime



somatotropin 

Take 0.17 mg/kg-0.24 mg/kg given in a week i.e 0.024 mg/kg -0.034 mg/kg daily



https://www.ncbi.nlm.nih.gov/books/NBK425701/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386113/#

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