Non-insulin dependent diabetes mellitus in a prepubertal child with Prader-Willi syndrome.

Diabetes mellitus has only rarely been reported in prepubertal children with Prader-Willi syndrome. All reported children have required insulin therapy. We report the development of a previously unrecognized association of non-insulin dependent diabetes mellitus in an obese 6 year-old child with Prader-Willi syndrome. She has never developed ketosis or acidosis, and she has been treated with oral hypoglycemic medication.

Prediction of neonatal hyperthyroidism in infants born to mothers with Graves disease.

OBJECTIVE: To determine whether determinations of thyrotropin-receptor antibody (TRAb) levels in newborn infants of women with Graves disease would predict which infants will have hyperthyroidism. METHODS: The TRAb levels, assayed in the sera of 14 infants born to 14 women with Graves disease, were measured sequentially in the infants with hyperthyroidism during the course of antithyroid medication therapy. RESULTS: Seven infants had TRAb values less than 0.15 and remained euthyroid. In seven infants whose initial TRAb values were more than 0.25 (range, 0.48 to 0.88), clinical and biochemical signs of hyperthyroidism developed. The infants were treated with antithyroid medication until day 57 to day 123 of life. Therapy was discontinued when the infants were free of symptoms and when serum thyroxine and triiodothyronine and free thyroxine levels remained normal during therapy with decreasing doses of antithyroid medication. When the medication was discontinued, TRAb values were less than 0.20. CONCLUSIONS: Infants born to mothers with Graves disease with initial TRAb values less than 0.15 remained euthyroid. The TRAb values greater than 0.25 were associated with the development of neonatal hyperthyroidism. During treatment of neonatal hyperthyroidism, TRAb values less than 0.20 may be helpful in deciding when to withdraw antithyroid medication.

Detection of human growth hormone receptors on IM-9 cells and peripheral blood mononuclear cell subsets by flow cytometry: correlation with growth hormone-binding protein levels.

We have developed a method using flow cytometry to identify fluorescein-conjugated GH receptors (GHR) on IM-9 lymphocytes and circulating peripheral blood mononuclear cell subsets. Binding to IM-9 cells and peripheral blood mononuclear cells was concentration dependent and could be competitively blocked by the addition of unlabeled human GH, but not by the addition of rat or bovine GH or human insulin or PRL. Using two-color flow cytometric analysis, fluorescein-conjugated human GHR were readily detected on more than 90% of B lymphocytes and monocytes, but only variably on T lymphocytes. B Lymphocytes and monocytes had approximately 6000 GHR/cell. Using two-color flow cytometry, we identified GHR on circulating B lymphocytes in subjects with GH deficiency (n = 9), precocious puberty (n = 6), and Turner syndrome (n = 5) and in seven subjects with miscellaneous disorders, including familial short stature, bone dysplasia, Crohn disease, congenital adrenal hyperplasia, and acromegaly. The percentage of B lymphocytes expressing GHR in subjects with GH deficiency (mean +/- SD, 95 +/- 9%), precocious puberty (91 +/- 15%), and Turner syndrome (84 +/- 15%) was not different from that in normal volunteers (90 +/- 12%; n = 14). In 10 subjects, serum GH-binding protein levels were assayed simultaneously with B lymphocyte GHR. GH-binding protein was normal in all (mean, 1255 pmol/L; range, 773-1809). There was a good correlation between GHR expression on B lymphocytes and GH-binding protein levels (r = 0.75; P = 0.01). We postulate that GHR found on circulating B lymphocytes may contribute to the pool of receptors identified in serum as GH-binding proteins. Two-color flow cytometry appears to be an effective method for the detection of GHR on circulating peripheral blood mononuclear cell subsets. The evaluation of GHR on circulating B lymphocytes may prove to be a useful means of evaluating GH-GHR interactions in subjects with growth disorders.

Subacute combined degeneration of the spinal cord: MRI detection of preferential involvement of the posterior columns in a child.

Subacute combined degeneration of the spinal cord (vitamin B12-deficient myelopathy) is a neurologic disorder manifesting progressive symptoms of paresthesia and spastic paralysis. As shown by pathology, it initially involves the posterior columns of the thoracic cord. We present a case of vitamin B12 deficiency with preferential posterior column involvement of the thoracic cord in a child. Theoretically, this should be the earliest, most reversible stage of the disease, making recognition of this MRI pattern of critical importance.

Hyperthyroidism.

Hyperthyroidism in children and adolescents usually is due to Graves disease. The diagnosis may not be recognized promptly, and clinical findings initially may be attributed incorrectly to cardiac or psychological disorders. Once suspected, history and physical findings and measurements of TSH level, thyroid hormone levels, and thyroid antibodies make the diagnosis apparent. Treatment varies among endocrinologists and includes antithyroid medication, surgery, and radioactive iodine. Much is being learned about the autoimmune response that causes the disease, and the hope is that therapies directed at altering the autoimmune abnormalities ultimately will offer the best therapeutic alternatives.

New-onset IDDM presenting with diabetic ketoacidosis in a pregnant adolescent.

OBJECTIVE: To describe the presentation of insulin-dependent diabetes mellitus (IDDM) as ketoacidosis during pregnancy in a teenager. CASE: A 14-year-old pregnant girl presented with ketoacidosis (bicarbonate 14 nM, 14 meq/l, pH 7.27, glucose 67 mM, 1,208 mg/dl) during the last month of pregnancy with a fetal demise. Two years of follow-up has confirmed that she has IDDM. CONCLUSIONS: Diabetes presenting in pregnant adolescents is likely due to IDDM. Immediate insulin therapy and proper education about managing diabetes should be initiated to hopefully prevent the outcome described in this patient.

Implications of the DCCT for children and adolescents with IDDM.

The DCCT findings have unique implications for youth with diabetes. Attempts should be made to achieve improved glycemic control in all children and adolescents with diabetes, but particular care needs to be exercised to avoid untoward side effects, especially hypoglycemia.

Thyrotropin-releasing hormone stimulation tests in infants.

The TSH response to TRH administration (7 micrograms/kg) was measured in 68 infants (22 premature) who had abnormal thyroid screening tests by the filter paper method and whose serum thyroid function tests were only mildly abnormal. Twenty-eight infants (12 premature) had peak TSH values of 35 mU/L or less and were considered normal (group I). Forty infants (10 premature) had peak TSH values above 35 mU/L and were considered hyperresponsive (group II). The mean age at testing, screening T4, TSH levels that prompted the testing, as well as baseline T4, T3, and free T4 at the time of TRH testing were not different between the groups. The mean (+/- SD) baseline TSH value was greater in group II (6.8 +/- 2.3 mU/L) than in group I (4.4 +/- 2.2 mU/L; P < 0.001). However, there was a great deal of overlap in the individual TSH values (group I, 0.9-10 mU/L; group II, 1.9-10.6 mU/L). Mean peak TSH levels were significantly different in the two groups (group I, 24 +/- 7.7 mU/L; group II, 60.3 +/- 26.1 mU/L; P < 0.001). During long term follow-up, all 25 group I infants available for evaluation have been confirmed as clinically and biochemically normal. No infant diagnosed as normal was later found to have evidence of hypothyroidism. Fourteen infants in group II have had evidence of thyroid dysfunction. We conclude that the TSH response to TRH stimulation is a useful tool for the evaluation of infants suspected of having primary hypothyroidism. Whether hyperresponsiveness to TRH represents a form of neonatal hypothyroidism requiring treatment remains to be determined.

Familial Pallister-Hall syndrome: case report and hormonal evaluation.

Pallister-Hall syndrome is a usually lethal dysplasia/malformation syndrome characterized by hypothalamic hamartoblastoma, hypopituitarism, postaxial polydactyly, craniofacial malformations, imperforate anus, and other malformations. We report a familial case in a male infant and his female sib fetus, suggesting autosomal recessive inheritance, or germinal mosaicism for an autosomal dominant mutation, or a segregating submicroscopic chromosome abnormality. Detailed endocrine evaluation on the surviving infant revealed documented pituitary function, pituitary deficit, and hypothalamic deficiency. We suggest that hypothalamic dysfunction contributes to the hypopituitarism seen in Pallister-Hall syndrome.

Inappropriate suppression of thyrotropin during medical treatment of Graves disease in childhood.

Twenty-nine patients (22 female) aged 2 to 17 years were followed with serial measurements of serum triiodothyronine, thyroxine, and thyrotropin during medical therapy for Graves disease. Fourteen patients had 17 instances of hypothalamic-pituitary-thyroid suppression with inappropriately low thyrotropin levels. Five patients had six episodes of low thyroxine and triiodothyronine levels with normal levels of thyrotropin, and 10 patients had 11 episodes of normal thyroxine and triiodothyronine levels with subnormal levels of thyrotropin. We conclude that thyrotropin values may not be reliable for diagnosing either mild hypothyroidism or persistent hyperthyroidism during the medical treatment of Graves disease.

46,XX pure gonadal dysgenesis with growth hormone deficiency and impaired 3 beta-hydroxysteroid dehydrogenase activity.

Patients with 46,XX pure gonadal dysgenesis generally are of normal stature and have less than usual amounts of pubic and axillary hair. We report on a patient who presented at age 11.9 years with short stature, absence of breast development, and excessive pubic hair. Her karyotype in leukocytes, fibroblasts, and streak gonad was 46,XX. The patient was diagnosed as having growth hormone deficiency. Elevated ACTH stimulated levels of 17-hydroxypregnenolone and dehydroepiandrosterone and elevated ACTH stimulated ratio of 17-hydroxypregnenolone to 17-hydroxyprogesterone suggested inadequate adrenal 3 beta-hydroxysteroid dehydrogenase activity. Treatment with growth hormone resulted in improvement in growth velocity and replacement with estrogen in feminization. We suggest that the finding of short stature in patients with 46,XX pure gonadal dysgenesis should not be attributed to the syndrome, but rather requires investigation for possible growth hormone deficiency. The poor growth of our patient prior to growth hormone replacement implies that dehydroepiandrosterone, unlike testosterone and estrogen, is ineffective in promoting linear growth in the absence of adequate growth hormone.

Diabetic ketoacidosis. Neurologic collapse during treatment followed by severe developmental morbidity.

Diabetic Ketoacidosis (DKA) remains the leading cause of death in children with type 1 diabetes mellitus. Complications occurring during DKA treatment include cerebral edema and neurologic collapse. Developmental outcomes following neurologic deterioration during DKA have varied from no sequelae to severe developmental disabilities. A total of three children developed neurologic deterioration during treatment of DKA at Buffalo Children's Hospital between 1984 and 1987. The authors treated aggressively for cerebral edema. Characteristic findings on the computed tomography (CT) scans and magnetic resonance imaging (MRI) of the brain included hemorrhagic infarctions of the thalami, basal ganglia and lentiform nuclei. The authors conducted developmental follow-up examinations between 1-1/2 - 3 years following recovery from DKA coma. Although they noted significant recoveries over time, developmental disabilities persisted. The clinical courses and neuroradiographic findings of these patients are compatible with sequelae of central brain stem herniation and cytotoxic brain injury. Continued efforts are needed in the prevention and early detection of clinically significant cerebral edema during treatment of DKA.

Vocational adjustment and general well-being of young adults with IDDM.

The vocational experiences and general well-being of 58 young adult subjects (mean age 24.3 yr) with insulin-dependent diabetes mellitus (IDDM) diagnosed during their adolescence were compared with that of 55 healthy matched control subjects with linear logistic discriminant function analyses. Assessment measures included the Rand General Well-Being Scale and the Rand Functional Limitations and Physical Abilities Batteries. Diabetic subjects, on average, reported significantly lower general well-being than control subjects, particularly in terms of health-related fears and feelings of depression. However, diabetic subjects did not report a pervasive functional deficit relative to control subjects and experienced similar employment rates and problems in the workplace. These results suggest that this group of young adult diabetic subjects has adjusted well to the demands of the workplace despite lower reports of general well-being. The results are discussed in light of relevant sampling issues.

Prolonged survival without therapy in congenital adrenal hypoplasia.

A diagnosis of congenital adrenal hypoplasia was established in a male child at 3 years of age. Although there was biochemical evidence of mineralocorticoid deficiency when he was 2 months old, no definite glucocorticoid deficiency was demonstrated. The child thrived well without replacement hormone therapy until he contracted an illness associated with vomiting. Subsequent tests confirmed the existence of both glucocorticoid and mineralocorticoid deficiencies due to adrenal hypoplasia. This case and the other reported in the literature point out that the glucocorticoid deficiency in congenital adrenal hypoplasia may become progressively more severe with time. Congenital adrenal hypoplasia may be the correct diagnosis in cases mistakenly diagnosed as acquired adrenal insufficiency.

Responses to continuous and intermittent exercise in healthy and insulin-dependent diabetic children.

The hormonal (growth hormone, glucagon, cortisol) and metabolic (glucose, ketone bodies) responses to 30 min of continuous vs 30 min of intermittent exercise were evaluated in five male children with insulin-dependent diabetes mellitus (IDDM) and five healthy male children. Each subject performed both types of exercise. In the healthy children, growth hormone levels rose, and glucose, glucagon, cortisol, and ketone bodies remained unchanged during both continuous and intermittent exercise. In the IDDM subjects, the mean reductions in glucose concentration were 99 mg% and 84 mg% during continuous and intermittent exercise, respectively. The levels of cortisol and ketone bodies in the IDDM subjects were significantly (P less than 0.05) elevated above the values obtained in the healthy subjects irrespective of the type of exercise. The mean concentrations of growth hormone, glucagon, cortisol, and ketone bodies were not significantly different between continuous and intermittent exercise. The study concludes that in healthy children the hormonal and metabolic responses to a continuous and an intermittent exercise protocol are similar. In the IDDM subjects, however, both forms of physical activity are associated with a decline in plasma glucose and no significant differences in hormonal and metabolic responses.

17 alpha-hydroxylase deficiency in a genetic male and female sibling pair.

The diagnosis of congenital adrenal hyperplasia due to a deficiency of the enzyme 17 alpha-hydroxylase was made in a genetic male and female sibling pair born of parents who were first cousins. The genetic male was a phenotypic female who presented with primary amenorrhea and mild hypertension. The genetic female exhibited absence of secondary sexual characteristics and severe hypertension. The plasma steroid data confirmed the diagnosis of 17 alpha-hydroxylase deficiency in both subjects: low 17 alpha-hydroxyprogesterone, elevated desoxycorticosterone, elevated corticosterone and elevated progesterone. These are the first case reports of 17 alpha-hydroxylase deficiency in a male-female sibling pair, and they add support to the hypothesis that this is an autosomal recessive disorder.