Many studies have shown impaired basal and/or
stimulated growth hormone secretion in depressed individual(1-3).
However, clinical consequences of depression in growth hormone secretion
and linear growth have not been clearly documented yet. Here we report a
child with short stature associated with impaired growth hormone
secretion and severe depression.
Case Report
This nine-year-old girl was referred to our clinic
with the chief complaint of short stature. She had been healthy and
developmentally normal until three years prior to the presentation. She
grew very poorly since six years of age, which coincided with the time
when her father was murdered and three weeks later and she witnessed her
mother’s suicide. Subsequently, her paternal uncle adopted her and her
five-year old younger brother. She was also noted to be significantly
introvert after the loss of her parents
On initial physical examination, her weight and
height were 17 kg and 108 cm respectively, both significantly below 5th
centile. Her height standard deviation score was –4.0 with a body mass
index of 14.6. Her upper-to-lower segment ratio was 1.1. She was
prepubertal. The rest of the physical examination was unremarkable.
On laboratory examination, her complete blood count,
urine analysis, thyroid function tests and biochemistry screening panel
(glucose, BUN, creatinin. Na, K, Cl, ALT, AST, calcium, phosphate,
alkaline phosphatase, iron, total iron binding capacity) were within
normal limits.
Her bone age was of five years old female. A child
psychiatry consultation revealed that she had frequent episodes of
sobbing and nightmares, sadness, forgetfulness, irrita-bility; poor
appetite and lack of interest and participation in play with peers ever
since the loss of her parents. She failed in school in first grade when
she was seven years old. However, she was an average student in the
following school years. Her score on Child Depression Inventory, adopted
for Turkish children was 29(4,5). Diagnosis of major depressive disorder
and post-traumatic stress disorder were made according to DSM–4(6). An
anti-depressant, fluoxetine at a dose of 10 mg/day was initiated because
of anticipated difficulty in follow-up because of the family’s remote
location (approximately 450 kilo-meters to our clinic) and poor
therapeutic alliance with new parents. Interview with the adopted
parents did not indicate any adverse family situation other than poor
economic and educational status. Upon determining an annualized growth
rate of 2 cm/year in her six months follow-up visit, two growth hormone
stimulation tests were planned. She felt better with anti- depressant
treatment during the interval and she self-discontinued the medication
three months after the initiation. Psychiatric evaluation confirmed some
degree of improvement in her mental health, though she was still
depressed. She was urged to restart fluoxetine and return to the child
psychiatry clinic in three months.
However, she was lost to follow-up until the age of
11˝ year. Detailed interval history revealed that she had never resumed
fluoxetine. The poor compliance with the clinical visits and fluoxetine
was explained by the family with low income, remote location, perceived
improving mental health and growth. On psychiatric evaluation, however,
she was essentially the same as the previous visit. She was again
recommended to start fluoxetine. At that time, her height was 116 cm
(height standard deviation score: –4.6) with a weight of 20 kg (body
mass index: 14.9). Her bone age was 7 years. She grew 7 cm in 23 months,
which represented a growth velocity of 3.6 cm/year. Two growth hormone
stimulation tests with L-dopa and insulin generated the peak levels of
16.6 and 9.6 ng/mL respectively. The insulin like growth factor –1 level
was low at 70 ng/mL (normal range: 120-328). Since she passed the tests
while growing poorly, a 5-hours nighttime growth hormone sampling via an
indwelling catheter every half-hour from 10 PM until 3 AM was performed.
Her highest growth hormone peak was 3.6 ng/mL with a mean integrated
concentration of 1.1 ng/mL. This was thought to be consistent with
growth hormone neurosecretory dysfunction and growth hormone treatment
was initiated at a dose of 0.045 mg/kg/day(7). She grew 4 cm during the
following six months. This time she complied with both medications. Her
psychiatric evaluation was found normal and fluoxetine was discontinued.
She regular1y kept her appointments in the pediatric endocrinology and
child psychiatry clinics. At the age of about 13 years on her last
visit, her height was 127 cm and her weight was 24.5 kg (body mass
index: 15.3). She grew 11 cm in 16 months while on growth hormone
treatment, which corresponds to a growth velocity of 8.2 cm/year. Her
height standard deviation score improved to –4.0. Her bone age was 8
years with a predicted adult height between 25 and 50th centile. Her
depression has not recurred.
Discussion
The appearance of growth failure in this patient
coincides to a major psychological trauma, which evidently led to a
severe depression. Her history, physical examination and laboratory
work-up failed to demonstrate any other medical problem to account for
her growth failure and short stature. Therefore, her documented severe
and long-standing depression remains to be the only explanation for her
growth problem. The underlying mechanism of growth failure in
association with depression is unclear. Suboptimal nutrition due to
poor appetite, which is common in patients with depression, could not be
excluded in this case because of unavailability of the premorbid weight
record, even though she maintained a normal and almost constant body
mass index while under our care. Her low insulin like growth factor –1
levels, normal growth hormone response to pharmacological stimulation
and subnormal basal integrated nighttime growth hormone secretion are
consistent with neurosecretory dysfunction, which refers to a subgroup
of short and slowly growing children with normal growth hormone
responses to classical stimuli but impaired spontaneous growth hormone
secretion with low insulin like growth factor –1 levels(7).
It has been assumed that these subjects have
inadequate spontaneous growth hormone secretion due to neuroendocrine
abnormalities. The secretion of growth hormone is regulated through a
complex neuroendocrine control system, especially by the functional
interplay of two hypothala- mic hormones, growth hormone-releasing
hormone and somatostatin. The two-hypo-thalamic neurohormones are
subject to modulation by a variety of neurotransmitters including
norepinephrine and seratonin(8). Lower activities of these
neurotransmitters are believed to be associated also with clinical
depression(9) .There has been sample evidence in the literature
indicating disordered growth hormone secretion in depression. Many
studies have shown impaired basal and/or stimulated growth hormone
secretion in depressed children and adults(1-3). Of note, in one study,
10 adult subjects with major depressive illness showed a growth hormone secretory pattern consistent with growth hormone neuro-secretory
dysfunction(10). However, none of those studies integrated growth data.
More-over, there have been no published cases of short stature resulting
from growth hormone deficiency due to depression. The reason may be that
most depressive episodes in children last too short to cause a
clinically obvious growth retardation. However, depression in children,
when untreated may last 7-9 months; 6-10% of the cases persist even
longer as in the present case(11).
The diagnosis in this case should not be confused
with psychosocial short stature. The hallmarks of psychosocial short
stature other than short stature abusive home environment and bizarre
behavior (e.g., polyuria, drinking from the toilet, stealing
food, encopresis, pain agnosia, self-abuse) were not present in this
case. Another inconsistent feature is her good response to growth
hormone treatment, which is typically not observed inpatient with
psychosocial short stature(12). Nevertheless, depression and poor growth
rates are the common features between our case and the subjects of Ferholt, suggesting regardless of the etiopathogenesis depression may
cause clinically overt growth failure, provided it lasts sufficiently
long.
Contributors: NOM collected data and literature.
AA and GO interpreted the case findings and planned management. AKT and
NOM drafted the manuscript. All the authors finally approved the paper.
Funding: None.
Competing interests: None stated.
