Transcript Hypopituitarism

Hypopituitarism
Objectives of this lecture
Definition
Causes
Clinical features: congenital and acquired
Diagnosis
Treatment and adverse effects
Hypopituitarism
Hypopituitarism : underproduction of growth hormone (GH) alone or in
combination with deficiencies of other pituitary hormones.
Affected children have postnatal growth impairment that is specifically
corrected by replacement of GH.
The incidence of hypopituitarism is between 1 in 4,000 and 1 in 10,000 live
births.
Aetiology
MULTIPLE PITUITARY HORMONE DEFICIENCY
Genetic Forms
Acquired Forms
The most common lesion is the craniopharyngioma.
CNS germinoma, eosinophilic granuloma (histiocytosis), tuberculosis, sarcoidosis,
toxoplasmosis, meningitis, and aneurysms may also cause hypothalamic-
hypophyseal destruction.
Trauma, including shaken child syndrome, motor vehicle crash, traction at delivery,
anoxia, and hemorrhagic infarction, may also damage the pituitary, its stalk, or the
hypothalamus.
ISOLATED GROWTH HORMONE DEFICIENCY AND INSENSITIVITY
Genetic forms of GH deficiency
Acquired Forms:
the use of radiotherapy for malignancy, meningitis, histiocytosis,
and trauma.
GH insensitivity:
Abnormalities of GH receptor
Post – receptor forms of GH insensitivity
CLINICAL MANIFESTATIONS:
Congenital hypopitutarism:
The child with hypopituitarism is usually of normal size and weight at birth .
*Children with severe defects in GH production or action are more than 4 SD below
the mean by 1 yr of age..
*Infants present with neonatal emergencies such as apnea, cyanosis, or severe
hypoglycemia with or without seizures.
*Microphallus in boys provides an additional diagnostic clue.
*Prolonged neonatal jaundice is common.
*special faces:
*The head of the toddler is round, and the face is short and
*The nose is small, and the nasolabial folds are well developed.
*The eyes are somewhat bulging.
*The neck is short, and the larynx is small. The voice is high- pitched and
remains high after puberty.
*The extremities are well proportioned, with small hands and feet.
*Weight for height is usually normal,
*The genitalia are usually small for age, and sexual maturation may be
delayed or absent.
*Facial, axillary, and pubic hair usually is lacking, and the scalp hair is fine.
*Symptomatic hypoglycemia, usually after fasting, occurs in 10–15% of
children with panhypopituitarism and those with IGHD.
*Intelligence is usually normal.
Acquired hypopitutarism:
The child initially is normal; manifestations similar to those seen in
idiopathic pituitary growth failure gradually appear and progress.
When complete or almost complete destruction of the pituitary gland
occurs, signs of pituitary insufficiency are present.
Atrophy of the adrenal cortex, thyroid, and gonads results in loss of
weight, asthenia, sensitivity to cold, and absence of sweating.
Sexual maturation fails to take place or regresses if already present.
There is a tendency to hypoglycemia. Growth slows dramatically.
*If the lesion is an expanding tumor, symptoms such as headache, vomiting,
visual disturbances, pathologic sleep patterns, decreased school
performance, seizures, polyuria, and growth failure may occur.
*Slowing of growth may antedate neurologic signs and symptoms, especially
with craniopharyngiomas, but symptoms of hormonal deficit account for
only 10% of presenting complaints.Evidence of pituitary insufficiency may
first appear after surgical intervention.
*In children with craniopharyngiomas, visual field defects, optic atrophy,
papilledema, and cranial nerve palsy are common.
LABORATORY FINDINGS:
The diagnosis of GH deficiency is suspected in children with moderate to severe
postnatal growth failure.
Criteria for growth failure include height below the 1% for age and sex, or height
more than 2 SD below sex-adjusted mid-parent height.
Acquired GH deficiency can occur at any age; when it is of acute onset, height may be
within the normal range but growth velocity decline.
A strong clinical suspicion is important in establishing the diagnosis because
laboratory measures of GH sufficiency lack specificity.
Definitive diagnosis of GH deficiency traditionally requires demonstration of absent or
low levels of GH in response to stimulation.
A variety of provocative tests have been devised that rapidly increase the level of GH
in normal children. These include administration of insulin, arginine, clonidine, or
glucagon.
In chronic GH deficiency, the demonstration of poor linear growth, delayed
skeletal age, and peak levels of GH (<10 ng/mL) in each of 2 provocative tests,
are compatible with GH deficiency.
In acute GH deficiency, a high clinical suspicion of GH deficiency and low peak
levels of GH (<10 ng/mL) in each of 2 provocative tests are compatible with GH
deficiency.
A majority of normal prepubertal children fail to achieve GH values >10 ng/mL with
2 pharmacologic tests. Three days of estrogen priming may be needed prior to GH
testing to achieve greater diagnostic specificity.
*In addition to establishing the diagnosis of GH deficiency, it is necessary to examine
other pituitary functions.
Levels of TSH, thyroxine (T4), ACTH, cortisol, gonadotropins, and gonadal steroids
may provide evidence of other pituitary hormonal deficiencies.
*The defect can be localized to the hypothalamus if there is a normal
response to the administration of hypothalamic-releasing hormones for
TSH, ACTH, or gonadotropins.
RADIOLOGICAL FINDINGS:
Skeletal maturation (bone age) is delayed in patients with IGHD and may be
even more delayed when there is combined GH and TSH deficiency.
CT is appropriate for recognizing suprasellar calcification associated with
craniopharyngiomas and bony erosions accompanying histiocytosis.
MRI provides a much more detailed view of hypothalamic and pituitary
anatomy.
DIFFERENTIAL DIAGNOSIS:
There are many causes of growth disorders :
1. Genetic short stature: one or both parents are short, with normal bone
age.
2. Systemic conditions: such as inflammatory bowel disease, celiac disease,
occult renal disease, and anemia must be considered.
Patients with systemic conditions often have greater loss of weight than
length.
3.idiopathic short stature: A few otherwise normal children are short (>3 SD
below the mean for age) and grow 5 cm/yr or less but have normal levels
of GH in response to provocative tests and normal spontaneous episodic
secretion. Most of these children show increased rates of growth when
treated with GH in doses comparable to those used to treat children with
hypopituitarism.
Plasma levels of IGF-I in these patients may be normal or low.
4. Constitutional growth delay:
a common variant of normal growth.
Length and weight measurements of affected children are normal at birth, and
growth is normal for the first 4–12 mo of life. Height is sustained at a lower
percentile during childhood.
The pubertal growth spurt is delayed, so their growth rates continue to decline
after their friends have begun to accelerate.
Detailed questioning often reveals other family members (frequently 1 or both
parents) with histories of short stature in childhood, delayed puberty, and
eventual normal stature.
IGF-I levels tend to be low for chronological age but within the normal range for
bone age.
Growth hormone responses to provocative testing tend to be lower than in
children with a more typical timing of puberty.
The prognosis for normal adult height in these children is good. Boys with
more than 2 yr of pubertal delay may benefit from a short course of
testosterone therapy to hasten puberty after 14 yr of age.
The cause of this variant of normal growth is thought to be persistence of the
relatively hypogonadotropic state of childhood .
5. Primary hypothyroidism: is more common than GH deficiency. Low total or
free T4 and elevated TSH levels establish the diagnosis. Responses to GH
provocative tests may be subnormal.
Because thyroid hormone is a necessary for normal GH synthesis, it must
always be assessed before GH evaluation.
6. Psychosocial dwarfism:
Emotional deprivation is an important cause of retardation of growth and mimics
hypopituitarism.
The condition is known as psychosocial dwarfism, maternal deprivation dwarfism,
or hyperphagic short stature.
Functional hypopituitarism is indicated by low levels of IGF-I and by inadequate
responses of GH to provocative stimuli.
Puberty may be normal or even premature in its appearance. Appropriate history
and careful observations reveal disturbed mother-child or family relations and
provide clues to the diagnosis
Proof may be difficult to establish because the parents often hide the true family
situation from professionals, and the children rarely can talk.
Emotionally deprived children frequently have abnormal or voracious appetites,
enuresis, encopresis, insomnia, crying spasms.
TREATMENT:
In children with classic GH deficiency, treatment should be started as soon
as possible to narrow the gap in height between patients and their peers
during childhood and to have the greatest effect on mature height.
The recommended dose of hGH is 0.18–0.3 mg/kg/wk during childhood.
Higher doses have been used during puberty. Recombinant GH is
administered subcutaneously in 6 or 7 divided doses. Growth hormone
therapy should be continued until near final height is achieved.
Some patients develop either primary or central hypothyroidism while under
treatment with GH. Similarly, there is a risk of developing adrenal
insufficiency, If unrecognized, this can be fatal.
Periodic evaluation of thyroid and adrenal function is indicated for all
patients treated with GH.
*Recombinant IGF-I is approved for use in the United States. It is given
subcutaneously twice a day. The risk of hypoglycemia is reduced by giving
the injections concurrently with a meal or snack.
In certain situations, its use will be more effective than use of GH.
GH is currently approved in the United States for treatment of children with
growth failure as a result of Turner syndrome, end-stage renal failure
before kidney transplantation, Prader-Willi syndrome, intrauterine growth
retardation, and idiopathic short stature.
In children with MPHD, replacement should also be directed at other
hormonal deficiencies.
ADVERSE EFFECTS OF hGH TREATMENT:
*Some patients treated with GH have developed leukemia.
Growth hormone treatment does not increase the risk for recurrence of brain
tumors or leukemia.
*Other reported side effects include pseudotumor cerebri, slipped capital femoral
epiphysis, gynecomastia, and worsening of scoliosis.
*There is an increase in total body water during the first 2 wk of treatment.
*Fasting and postprandial insulin levels are characteristically low before treatment,
and they normalize during GH replacement.
Treatment does not increase risk of type 1 diabetes, but it may increase the risk
of type 2 diabetes.