Severe unsuspected maternal hypothyroidism discovered after the diagnosis of thyrotropin receptor-blocking antibody-induced congenital hypothyroidism in the neonate: failure to recognize and implications to the fetus.

BACKGROUND: Whereas most adequately treated children with congenital hypothyroidism (CH) do well neurodevelopmentally, when both the maternal and fetal thyroid glands are compromised, significant cognitive delay can occur despite early and aggressive postnatal therapy. Maternal thyrotropin-stimulating hormone receptor (TSHR)-blocking antibodies (Abs) can be transmitted to the fetus and cause combined maternal-fetal hypothyroidism. Current guidelines recommend their measurement only if mothers have known autoimmune thyroid disease, there is a history of a previously affected sibling, or when transient CH is suspected. RESULTS: We report 3 infants in whom the diagnosis of maternal hypothyroidism was not known and was identified only after CH was diagnosed in their babies. One of these infants had developmental delay despite rapid normalization of thyroid function postnatally. All 3 mothers had potent TSHR Abs in serum, but thyroid peroxidase Abs and thyroglobulin Abs were detectable in only 2 of them. CONCLUSIONS: TSHR-blocking Ab-induced CH should be suspected in any baby with CH irrespective of the known family history, especially if the hypothyroidism is severe and a eutopic thyroid gland is demonstrated on imaging. Measurement of TSHR Abs is necessary to establish the diagnosis; the presence of other thyroid Abs is insufficiently sensitive and may miss some cases.

Growth hormone therapy in progeria.

Catabolic processes seen in Hutchinson-Gilford progeria resemble those of normal aging and, in the affected children, usually result in death at an early age. In addition to its growth promoting effects, growth hormone (GH) has potent anabolic properties. Administration of GH ameliorates some of the catabolic effects of normal aging. We report the results of GH treatment in a young child with progeria.

Development of diabetes mellitus in two boys after the initiation of growth hormone therapy.

In addition to its growth promoting properties, growth hormone (GH) has anti-insulin effects that could cause hyperglycemia. Development of diabetes mellitus as a result of GH therapy has been an ever-present, albeit rarely reported, concern. This report is that of two adolescent boys who developed diabetes mellitus after the initiation of treatment with GH.

A provisionally unique syndrome of macrosomia, bone overgrowth, macrocephaly, and tall stature.

We report a young man with intrauterine macrosomia, macrocephaly, and bony abnormalities. Excessive growth continued throughout infancy and childhood. Bone age was advanced. He developed contractures of the large joints and was confined to a wheelchair. Extensive laboratory studies, repeated on multiple occasions were all normal. Intellectually, he was normal. His near final height was 234 cm. The constellation of findings in this patient is at variance with previously described syndromes of tall stature. We postulate that excessive size and bone overgrowth in this young man is caused by a receptor/post-receptor abnormality involving a growth on/off mechanism at the cellular level.

Simultaneous occurrence of neurofibromatosis type 1 and tuberous sclerosis in a young girl.

Neurofibromatosis type 1 and tuberous sclerosis are the two most common neurocutaneous disorders in humans. Both are transmitted as autosomal dominant conditions with a high rate of new mutations and similar clinical features. However, the two disorders have distinct and well-delineated genetic, biochemical, and physical findings. Simultaneous occurrence of these two conditions is rare. We report on a young girl who inherited both disorders, review similar cases reported in the world literature, and discuss possible implications of the presence of NF1 and TSC in the same individual.

Cortisol and estradiol secretion by a benign virilizing adrenocortical tumor in a prepubertal girl.

We report a 5.5 year-old girl with a benign adrenocortical adenoma who presented with virilization and rapid growth. She did not have any clinical features of isosexual precocity or, except for hypertension, Cushing's syndrome. Measurement of hormones in adrenal vein blood obtained at surgery showed high concentrations of testosterone, cortisol, estradiol and intermediary substrates. Elevated levels of hormones detected in the peripheral blood were released directly from the tumor and were not the result of peripheral interconversion. Hyperandrogenism can obscure the clinical features of Cushing's syndrome and estrogen hypersecretion in patients with functional adrenal tumors.

Endocrine gland abnormalities in thalassemia major: a brief review.

Thalassemia major (beta-thalassemia) affects a significant segment of the population in certain areas of the world. Alterations in migration patterns have changed the geographic distribution of this disease and made it a worldwide health problem. Over the course of the past 2-3 decades hypertransfusion therapy has significantly increased the life expectancy, and improved the quality of life of these patients. At the same time there has been an increase in the frequency of complications of this therapy caused by iron overload. Endocrine gland abnormalities contributed little to the morbidity or mortality of beta-thalassemia in the past. As a result of hypertransfusion therapy and increased longevity, however, endocrinopathies have become more common and contribute significantly to morbidity in these patients. In this article we briefly review the current understanding of endocrine gland abnormalities, primarily caused by iron overload, in patients with thalassemia major.