Growth hormone deficiency

Growth hormone deficiency (GHD), or human growth hormone deficiency, is a medical condition resulting from not enough

Even congenital GH deficiency does not usually impair length growth until after the first few months of life. From late in the first year until mid-teens, poor growth and/or shortness is the hallmark of childhood GH deficiency. Growth is not as severely affected in GH deficiency as in untreated hypothyroidism, but growth at about half the usual velocity for age is typical. It tends to be accompanied by delayed physical maturation so that bone maturation and puberty may be several years delayed. When severe GH deficiency is present from birth and never treated, adult heights can be as short as 48-65 inches (122–165 cm).^{[citation needed]}

Severe GH deficiency in early childhood also results in slower muscular development, so that gross motor milestones such as standing, walking, and jumping may be delayed. Body composition (i.e., the relative amounts of bone, muscle, and fat) is affected in many children with severe deficiency, so that mild to moderate chubbiness is common (though GH deficiency alone rarely causes severe obesity). Some severely GH-deficient children have recognizable, cherubic facial features characterized by maxillary hypoplasia and forehead prominence.^[5]

Other side effects in children include sparse hair growth and frontal recession, and pili torti and trichorrhexis nodosa are also sometimes present.^[6]: 501

Adults

Recognised effects include:^[7][8]

• Increased
  5-alpha-reductase
• Reduced sex hormone-binding globulin (SHBG)
• Reduced muscle mass and strength
• Baldness
  in men
• Reduced bone mass and osteoporosis (Decreased bone density)
• Reduced energy
• Impaired concentration and
  memory loss
• Increased body fat, particularly around the waistline
• LDL
  cholesterol
• Increased levels of fibrinogen and plasminogen activator inhibitor
• thickened intima media
• Lack of well-being
• Depression and anxiety
• Social isolation
• Fibromyalgia syndrome
• Neuromuscular dysfunction
• Central adiposity
• Decreased muscle mass
• Insulin resistance
• Accelerated
  atherogenesis
• Prothrombotic state
• Decreased
  sweating and thermoregulation
  .

• GHRHR
  , GH1)
• congenital diseases such as
  Prader-Willi syndrome, Turner syndrome,^[10] or short-stature homeobox gene deficiency^[11]
• congenital malformations involving the pituitary (e.g., septo-optic dysplasia
  , posterior pituitary ectopia)
• chronic kidney disease^[12]
• intracranial tumors in or near the sella turcica, especially craniopharyngioma
• damage to the pituitary from radiation therapy to the head (e.g. for leukemia or brain tumors), from surgery, from trauma, or from intracranial disease (e.g. hydrocephalus)
• autoimmune inflammation (hypophysitis)
• ischemic or hemorrhagic infarction from low blood pressure (
  Sheehan syndrome) or hemorrhage pituitary apoplexy

Although GH can be readily measured in a blood sample, testing for GH deficiency is constrained by the fact that levels are nearly undetectable for most of the day. This makes simple measurement of GH in a single blood sample useless for detecting deficiency. Physicians, therefore use a combination of indirect and direct criteria in assessing GHD, including:[17]

• Auxologic criteria (defined by body measurements)
• Indirect hormonal criteria (IGF levels from a single blood sample)
• Direct hormonal criteria (measurement of GH in multiple blood samples to determine secretory patterns or responses to provocative testing), in particular:
  • Subnormal frequency and amplitude of GH secretory peaks when sampled over several hours
  • Subnormal GH secretion in response to at least two provocative stimuli
  • Increased IGF1 levels after a few days of GH treatment
• Response to GH treatment
• Corroborative evidence of pituitary dysfunction

"Provocative tests" involve giving a dose of an agent that will normally provoke a pituitary to release a burst of growth hormone. An intravenous line is established, the agent is given, and small amounts of blood are drawn at 15-minute intervals over the next hour to determine if a rise of GH was provoked. Agents which have been used clinically to stimulate and assess GH secretion are

Severe GH deficiency in childhood additionally has the following measurable characteristics:[19]

• Proportional stature well below that expected for family heights, although this characteristic may not be present in the case of familial-linked GH deficiency
• Below-normal velocity of growth
• Delayed physical maturation
• Delayed bone age
• Low levels of
  IGF1
  , IGF2, IGF binding protein 3
• Increased growth velocity after a few months of GH treatment

In childhood and adulthood, the diagnosing doctor will look for these features accompanied by corroboratory evidence of hypopituitarism such as deficiency of other pituitary hormones, a structurally abnormal pituitary, or a history of damage to the pituitary. This would confirm the diagnosis; in the absence of pituitary pathology, further testing would be required.^{[citation needed]}

Classification

Growth hormone deficiency can be congenital or acquired in childhood or adult life. It can be partial or complete. It is usually permanent, but sometimes transient. It may be an isolated deficiency or occur in association with deficiencies of other

GH supplementation is not recommended medically for the physiologic age-related decline in GH/IGF secretion.[9]^[15] It may be appropriate in diagnosed adult-onset deficiency, where a weekly dose of approximately 25% of that given to children is given. Lower doses again are called for in the elderly to reduce the incidence of side effects and maintain age-dependent normal levels of IGF-1.^[24]

In many countries, including the UK, the majority view among endocrinologists is that the failure of treatment to provide any demonstrable, measurable benefits in terms of outcomes means treatment is not recommended for all adults with severe GHD,

1. Severe GH deficiency, defined as a peak GH response of <9mU/litre during an insulin tolerance test
2. Perceived impairment of quality of life, as assessed by questionnaire
3. They are already treated for other pituitary hormone disorders

Where treatment is indicated, duration is dependent upon indication.

Cost of adult treatment in the UK is 3000-4000 GBP annually.^[25]

Side effects

• Headaches
• Joint pain and muscle pain
• Fluid retention, and carpal tunnel syndrome
• Mild hypertension
• Visual problems
• Nausea and vomiting
• Paraesthesiae
• Antibody formation
• Reactions at the injection site
• Rarely,
  benign intracranial hypertension.^[9]

When treated with GH, a severely deficient child will begin to grow faster within months. In the first year of treatment, the rate of growth may increase from half as fast as other children are growing to twice as fast (e.g., from 1 inch a year to 4 inches, or 2.5 cm to 10). Growth typically slows in subsequent years, but usually remains above normal so that over several years a child who had fallen far behind in their height may grow into the normal height range. Excess adipose tissue may be reduced.[26]

Adults

GH treatment can confer a number of measurable benefits to severely GH-deficient adults, such as enhanced energy and strength, and improved bone density. Muscle mass may increase at the expense of adipose tissue. Although adults with hypopituitarism have been shown to have a reduced life expectancy, and a cardiovascular mortality rate of more than double controls,^[25] treatment has not been shown to improve mortality, although blood lipid levels do improve. Similarly, although measurements of bone density improve with treatment, rates of fractures have not been shown to improve.^[25]

Effects on quality of life are unproven, with a number of studies finding that adults with GHD had near-normal indicators of QoL at baseline (giving little scope for improvement), and many using outdated dosing strategies. However, it may be that those adults with poor QoL at the start of treatment do benefit.^[9]

Epidemiology

The incidence of

Like many other 19th century medical terms which lost precise meaning as they gained wider currency, "midget" as a term for someone with severe proportional shortness acquired pejorative connotations and is no longer used in a medical context.^[28]

Notable modern pop cultural figures with growth hormone deficiency include actor and comedian Andy Milonakis, who has the appearance and voice of an adolescent boy despite being in his 40s.^[29][30] Argentine footballer Lionel Messi was diagnosed at age 10 with growth hormone deficiency and was subsequently treated.^[31] TLC reality star Shauna Rae was affected by a medically-caused growth hormone deficiency resulting from childhood glioblastoma cancer treatment.^[32] Oscar winning actress Linda Hunt was diagnosed as having this condition when a teenager.

See also

• Hypothalamic–pituitary–somatic axis

References