The Brush Foundation studies on human growth and development, begun in 1931 and terminated in 1942, have been intensively reviewed and studied by Dr Greulich and Miss Pyle in the formulation of this Radiographic Atlas of Skeletal Development of the Hand and Wrist Serial radiographs of from 2 to 20 hand-films made at successive examinations of each of 1000 boys and girls made up the radiographic material Standards were selected that were judged to be the most representative of the central tendency or anatomic mode of each chronologic age group from birth through 18 years

Radiographic Atlas of Skeletal Development of the Hand and Wrist

Unrecognized congenital hypothyroidism leads to mental retardation. Newborn screening and thyroid therapy started within 2 weeks of age can normalize cognitive development. The primary thyroid-stimulating hormone screening has become standard in many parts of the world. However, newborn thyroid screening is not yet universal in some countries. Initial dosage of 10 to 15 g/kg levothyroxine is recommended. The goals of thyroid hormone therapy should be to maintain frequent evaluations of total thyroxine or free thyroxine in the upper half of the reference range during the first 3 years of life and to normalize the serum thyroid-stimulating hormone concentration to ensure optimal thyroid hormone dosage and compliance. Improvements in screening and therapy have led to improved developmental outcomes in adults with congenital hypothyroidism who are now in their 20s and 30s. Thyroid hormone regimens used today are more aggressive in targeting early correction of thyroid-stimulating hormone than were those used 20 or even 10 years ago. Thus, newborn infants with congenital hypothyroidism today may have an even better intellectual and neurologic prognosis. Efforts are ongoing to establish the optimal therapy that leads to maximum potential for normal development for infants with congenital hypothyroidism. Remaining controversy centers on infants whose abnormality in neonatal thyroid function is transient or mild and on optimal care of very low birth weight or preterm infants. Of note, thyroid-stimulating hormone is not elevated in central hypothyroidism. An algorithm is proposed for diagnosis and management. Physicians must not relinquish their clinical judgment and experience in the face of normal newborn thyroid test results. Hypothyroidism can be acquired after the newborn screening. When clinical symptoms and signs suggest hypothyroidism, regardless of newborn screening results, serum free thyroxine and thyroidstimulating hormone determinations should be performed.

/pdf/update-of-newborn-screening-and-therapy-for-congenital-1iyn578kad.pdf

Update of Newborn Screening and Therapy for Congenital Hypothyroidism

Conception is followed by a series of hormonal and metabolic changes that involve most maternal endocrine systems. With regard to thyroid metabolism, these include an increase in serum thyroxine-binding globulin and thyroid hormone concentrations, increased renal clearance of iodine, and increased production and turnover of thyroxine (T)1. Fetal and maternal thyroid physiology differ, but the systems interact by means of the placenta and amniotic fluid, which modulate the transfer of iodine and small but important amounts of thyroid hormone from mother to fetus1,2. In this article we shall review recent data and new insights regarding the changes . . .

Maternal and Fetal Thyroid Function

Objective: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). Evidence: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. Consensus Process: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. Recommendations: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy.

http://www.ispae.org.in/download_docs/2014_ESPE_Consensus_Guidelines_Congenital_Hypothyroidism.pdf

European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism.

Congenital hypothyroidism (CH) represents one of the most common preventable causes of mental retardation. The fetal hypothalamic-pituitary-thyroid axis begins to function by midgestation and is mature in the term infant at delivery. If fetal hypothyroidism develops, untoward effects may be demonstrated in certain organ systems, including the central nervous system and skeleton. However, most infants with CH appear normal at birth. Recent data suggest that the hypothyroid fetus is protected to a certain extent by placental transfer of maternal thyroid hormone; serum thyroxine (T 4 ) levels in the cord blood of athyroid fetuses approximate one third of maternal levels. 1 In addition, studies in animal models of hypothyroidism demonstrate increased levels of brain iodothyronine deiodinase, the enzyme which converts T 4 to triiodothyronine (T 3 ). In the hypothyroid fetus, this increased enzyme acting on T 4 of maternal origin is sufficient to produce near normal fetal brain T 3 concentrations. 2 Thus, it appears that early detection and treatment of congenital hypothyroidism should have the potential to completely reverse the effects of fetal hypothyroidism in all but the most severe cases, for example, athyreotic infants born to mothers with thyroid problems resulting in inadequate placental transfer of maternal thyroid hormone. Since the development of pilot screening programs for CH in Quebec and Pittsburgh in 1974, 3 newborn screening for CH has become routine in essentially all developed countries of the world and is under development in Eastern Europe, South America, Asia, and Africa. In North America it is estimated that more than 5 million newborns are screened, with approximately 1400 infants with congenital hypothyroidism detected annually.

https://pediatrics.aappublications.org/content/pediatrics/91/6/1203.full.pdf

Newborn Screening for Congenital Hypothyroidism: Recommended Guidelines

Detection of congenital hypopituitary hypothyroidism: ten-year experience in the Northwest Regional Screening Program.

To determine the benefit of collecting two routine specimens to test for congenital hypothyroidism, we examined the results of our newborn screening program during the last 9.5 years. The Northwest Regional Screening Program (NWRSP) performs a primary thyroxine test with thyroid-stimulating hormone determinations on the lowest 10% of dried blood filter paper specimens. An initial specimen is obtained in the newborn period, and a routine second specimen is collected at approximately 4 to 6 weeks of age in all infants born in Oregon and 25% of infants born in Idaho, Montana, Alaska, and Nevada. Between May 1975 and October 1984, 182 infants with primary hypothyroidism were detected from 811,917 infants screened, a prevalence rate of 1:4,461. The routine second specimen led to the diagnosis of 19 infants of 484,604 infants screened, a detection rate of 1:25,505. When infants detected by the second screen were compared with those detected by the first screen, they had higher thyroxine and lower thyroid-stimulating hormone concentrations on filter paper and serum specimens. When thyroid scanning was used, all but one infant detected by the second screen had some residual thyroid tissue, whereas 35% of infants detected by the first screen had thyroid aplasia. Skeletal maturation was more likely to be normal in infants detected by the second screen. These infants appear to have milder hypothyroidism due to a later age of onset or slower evolution of thyroid failure. At a cost of $31,881 per infant detected by the second screen, the NWRSP found it cost-effective to obtain a routine second specimen.

Screening for congenital hypothyroidism with specimen collection at two time periods: Results of the Northwest Regional Screening Program

Primary hypothyroidism, empty sella, and hypopituitarism.

To determine the etiology of delayed puberty in a referral population, we analyzed the clinical features and endocrine studies in 146 children seen between 1975 and 1985 whose pubertal onset was greater than 2 SD from the mean. Patients fell into 5 major categories: constitutional pubertal delay (46%), central nervous system problems resulting in hypothalamic-pituitary deficits (32%), primary gonadal failure (9%), underlying systemic disease (9%), and anatomic genitourinary tract anomalies (1.3%). Short stature was the most common presenting complaint both alone and as one of several complaints (84%), whereas delayed puberty as a single or one of several complaints was recognized in slightly less than half (43%) of our patients. Patients tended to be short, have a slow growth rate, eunuchoid body proportions and have a delayed bone age compared to means for chronologic age; these parameters corresponded better with means for bone age. Laboratory tests identified those with pituitary deficits and gonadal failure, but studies generally could not distinguish marked constitutional delay from isolated gonadotropin deficiency. Unlike previous surveys, most of our patients had constitutional delay often associated with a family history of delay, or an abnormality of the hypothalamicpituitary axis either idiopathic or secondary to an intracranial tumor as the etiology of delayed puberty. Address for reprints: Stephen LaFranchi, M.D. Department of Pediatrics Oregon Health Sciences University 3181 S.W. Sam Jackson Park Road Portland, OR 97201, USA. INTRODUCTION The exact mechanism initiating the onset of puberty and the factors which contribute to the normal variation in time of onset of puberty remain unknown /1,2/. The mean age for onset of pubertal changes in North American children is well-established as 10.8 years for girls and 11.6 years for boys, although normal variation includes children whose pubertal development begins as late as three years beyond the mean /3,4/. Delay in pubertal onset can represent normal variation, often related to familial patterns, but it can also be seen in conditions involving both central hypothalamic-pituitary and peripheral gonadal systems and as a result of underlying medical or anatomical conditions /5/. As there are no recent reports studying all children in a defined population with delayed puberty, we examined the presenting complaints and etiologic factors in patients with delayed puberty evaluated by our pediatric endocrinology group during the past ten years. We analyzed the relationship of growth parameters such as height, weight, growth rate, and body proportions to chronologic age and bone age, and reviewed laboratory studies obtaine during evaluation of patients. PATIENTS AND METHODS

Patricia L. Krainz

Papers

Detection of congenital hypopituitary hypothyroidism: ten-year experience in the Northwest Regional Screening Program.

Screening for congenital hypothyroidism with specimen collection at two time periods: Results of the Northwest Regional Screening Program

Primary hypothyroidism, empty sella, and hypopituitarism.

Etiology of Delayed Puberty in 146 Children Evaluated Over a 10 Year Period