番茄社区app

A 15-year-old young man presents to a clinic after being referred for assessment related to his short stature and delayed puberty. He is not in any distress, but clinicians note that he is obviously small for his age, with a height of 131.5 cm (51.8 inches/4.3 feet -- i.e., less than the third percentile) and weight of 25 kg (about 55 lbs, also less than the third percentile). His face is noticeably small and his voice is thin; he is very shy, but communicates intelligently. His occipitofrontal circumference is low at 54 cm.

Physical examination shows an arm span of 138 cm and arm span-to-height ratio of 1:1.05. His blood pressure is 80/50 mmHg, and heart sounds are normal.

The patient has infantile genitalia with a stretched penile length of 4.5 cm and testicular volume of 2 ml, and no pubic or axillary hair growth. Clinicians learn that he is the second of a set of twin boys. He was delivered full-term via spontaneous vaginal delivery. His parents note that he cried immediately after birth and his birth weight was normal at 3.2 kg. His neonatal period passed without any notable events, and he developed normally during his first year, as did his twin brother.

He is the fifth child in a two-parent family setting; his patents report that his elder siblings (three males and one female) developed normally and attained normal height for their age.

His parents explain that while they noticed that he was not growing as tall as expected by the time he turned 6 years old, they were not concerned until he reached the age of 15, when his short stature relative to his twin brother became embarrassing.

Clinicians review photographs of the twins as they were growing up, and determine that the difference in stature became noticeable at the age of 2 years and became very evident after the age of 6.

The patient has a bone age of 7 years and an AA hemoglobin genotype; serum electrolyte, urea, and creatinine are all normal, as is cranial computerized tomography (CT) scan. A hormonal profile reveals very low levels of serum testosterone, growth hormone (GH), adrenocorticotropic hormone, thyroxine, follicle-stimulating hormone (FSH), luteinizing hormone, fasting cortisol, and high thyroid stimulating hormone.

Clinicians conclude that the patient has panhypopituitarism and start him on hormone-replacement therapy with GH therapy, levothyroxine (Synthroid), and low-dose prednisolone.

Within the first 7 months of hormone-replacement therapy, assessment shows that the patient's height is increased by 2.5 cm and his weight is increased by 2 kg. His testicular volume is also increased to 3 ml, and he shows great improvement in his physical activity level.

Clinicians then add subcutaneous human chorionic gonadotropin to the treatment regimen.

At month 11 of hormone-replacement therapy, the team adds FSH to induce spermatogenesis, and after 1 year, repeat testing shows marked improvement in the patient's serum hormonal levels. Unfortunately, during the 2-year follow-up period, the patient's clinic attendance is sporadic, and his hormone therapy is thus erratic.

Hormone therapy is then stopped "abruptly," the case authors report, when the patient's family is unable to afford further treatment. Clinicians are unsuccessful in their efforts to get any assistance with the treatment costs from pharmaceutical companies within and outside the patient's native Nigeria.

The patient is eventually lost to follow-up, despite clinicians' attempts to reach him.

Discussion

Clinicians presenting this in the Pan African Medical Journal note that the prevalence of hypopituitarism in children is not well documented, but may account for fewer than three cases per million people per year.

Hypopituitarism can be congenital or acquired and may affect individuals of any age, and cases due to traumatic brain injury are likely underdiagnosed, the case authors write.

They note that based on evidence of early onset from the age of 2 years, the cause in this patient is most likely congenital, although perinatal asphyxia or traumatic birth injury cannot be completely ruled out in twin gestation and vaginal delivery. Similarly, due to the lack of access to genetic studies, possible genetic mutation cannot be ruled out.

Aside from the patient's height, his development was comparable to that of his twin, with normal educational achievement and cranial CT findings, and there were no dysmorphic features suggestive of Pallister-Hall syndrome.

Any disease that affects the pituitary gland or stalk or the hypothalamus can cause hypopituitarism, the authors note. Causes may be acquired due to infiltrative disorders such as tuberculosis, sarcoidosis, histiocytosis X, and lymphocytic hypophysitis, as well as tumors (craniopharyngioma, germinoma, glioma, astrocytoma).

Congenital causes listed by the case authors include:

• Perinatal injuries (birth asphyxia, traumatic deliveries)

• Interrupted pituitary stalk

• Absent or ectopic neurohypophysis

• Pallister-Hall syndrome (hypothalamic hamartoma, polydactyly)

• Genetic disorders (isolated GH deficiency, PIT1 and PROP1 mutations, septo-optic dysplasia, isolated gonadotropin deficiency)

• Developmental central nervous system defect (anencephaly, holoprosencephaly, pituitary aplasia or hypoplasia).

The authors emphasize that morbidity and mortality can largely be prevented if young patients with hypopituitarism receive early diagnosis and treatment with appropriate hormone-replacement therapy. Deficiencies in one or more eight pituitary hormones may present as symptoms of hypoglycemia or adrenal crisis (i.e., profound hypotension or severe shock), as well as short stature, delayed puberty, and osteoporosis leading to increased risk for fracture in adulthood.

Studies of have shown that without treatment, those who underwent spontaneous puberty reached a mean final height of 4.7 SD (range 3.9 to 6.0) below the population mean, while induced puberty was associated with a mean final height SD score of -3.1.

In contrast, treatment with traditional GH regimens (two to four injections a week) in children who underwent spontaneous puberty resulted in a final height SD score of -2.8 (range -1.5 to -4.7), while in those in whom puberty was induced, mean final height was -1.6 (range -1.1 to -2.4). The mean gain in final height score is therefore estimated at 1.5 to 2.0 in average cases, and 3.5 in extreme cases, those researchers found.

In children, GH deficiency contributes significantly to mortality and is associated with an increased hazard ratio over 3.0 for , the case authors note.

Regarding their patient, they say, the psychological trauma he experienced due to what he considered an embarrassingly short stature -- likely worsened by the contrast with his growing twin brother -- could have been avoided with earlier diagnosis and available funds for appropriate hormone-replacement therapy.

The needed yearly approximately $30,000 USD (about $2,500/month) to purchase hormones for hormone-replacement therapy remains a significant for many families, especially for this patient, where the limited family income is meant to take care of seven family members, the case authors state, also citing a similar cost burden for sickle cell disease in their country.

"Perhaps, the outcome could have been different if the patient ... was enrolled on NHIS" [Ghana's National Health Insurance Scheme] and had access to the needed replacement hormones and laboratory tests at very low cost, to enhance early presentation, diagnosis, and treatment compliance, the authors write.

They add: "Notwithstanding the erratic supply of hormones, the patient experienced an encouraging increase in height and weight within the first 7 months of growth hormone therapy but could not be sustained because of financial constraint. He did not have any clinical or biochemical feature of hypoglycemia or adrenal crisis during the 2 years therapy at the pediatric endocrinology clinic," and he was likely to have responded well to treatment.

Given that the high cost of hormone-replacement therapy is unaffordable for most patients in developing countries, "enrolling pediatric endocrine patients on NHIS and including the hormones on the NHIS drug list will be a great panacea," the case authors conclude.

Comment