McCune Albright Syndrome (MCAS): a case series.

McCune Albright Syndrome (MCAS) is an association of, Café-au-lait macules, polyostotic fibrous dysplasia and autonomous hyperfunctioning endocrinopathy. This is a rare disorder seen more commonly in females. We evaluated 7 (6F & 1M) cases under six years of age (4 months to 5.5 yrs) presenting with Café-au-lait spots, polyostotic fibrous dysplasia and/or sexual precocity. All the 7 cases had large Café-au-lait spots, radiologic features of polyostotic fibrous dysplasia were seen in 5 cases. Six girls had precocious puberty with large ovarian follicles and elevated S. Estradiol levels (14-65 pg/dl) with prepubertal gonadotropin levels in 5 of them. Medroxy-progrestrone acetate was used to treat the sexual precocity. Five girls on follow up for 6 months (6mo-16mo) showed cessation of menstrual episodes and regression of ovarian follicles in three, regression in breast size in one, and three girls continued to grow at a height velocity >95th centile for age. Skeletal lesions and skin features did not show any change. No other endocrinopathy was noted. Gonadotropin independent precocious puberty was the only endocrine affection seen in this series.

Hyperthyroidism in children.

This study was done to characterize the clinical features, laboratory parameters and response to therapy and outcome of childhood hyperthyroidism. The evaluation included history, examination, laboratory investigations: serum T3, T4, TSH, free T3, free T4 by RIA or immunochemiluminescence (IC), antithyroid antibodies by standard techniques, bone age (BA) by Greulich and Pyle's method, clinical and laboratory response to treatment, and follow-up of 15 children with hyperthyroidism seen in past eight years. Age of onset, presentation, nature and duration of symptoms, family history, anthropometry and signs of hyperthyroidism were recorded. There were 10 girls and 5 boys (2:1). Three families had a history of thyroid disorders. Mean ages of onset and presentation were 8.25 +/- 3.4 and 9.27 +/- 3.2 years respectively. Clinical features included weight loss, heat intolerance and sweating, diarrhoea, behavioral problems, ophthalmopathy and tachycardia. BA was advanced. Serum T3 (mean = 4.29 +/- 1.77 ng/mL), T4 (18.75 +/- 5.64 micrograms/dL), FT3 (7.11 +/- 4.58 pg/mL) and FT4 (2.93 +/- 0.29 ng/mL) were markedly elevated. TSH was suppressed. Anti-microsomal antibodies (AMA) and anti-thyroglobulin antibodies (ATG) were positive in five. They were started on standard treatment with carbimazole 0.5-0.7 mg kg-1. Clinical and biochemical euthyroidism was achieved within 2.5 to 6 months in all, after which the drug was tapered, however, they required treatment for 2 years to 7.5 years. Four children were retreated for relapse and are now euthyroid and off treatment. Childhood hyperthyroidism requires long term treatment and careful monitoring. This study shows a remission rate of 67%.

Autoimmune thyroid disease in childhood: a study of children and their families.

OBJECTIVE: To study the clinical and laboratory profile of children with autoimmune thyroid disease (AITD) and its familial prevalence. DESIGN: Clinical and investigative evaluation of 96 children and adolescents 5 to 16 years old suspected of having AITD based on clinical and family data and similar assessment of parents and siblings of 30 confirmed cases of AITD. SETTING and SUBJECTS: Of these 96 cases, 66 were from a private clinic and 30 were institution based thyroid antibody positive with confirmed AITD. On initial testing 36 (55%) of 66 clinic cases were thyroid antibodies (ab) positive and 30 were (ab) negative. In 12 of 30 ab -ve cases retesting for antibodies by newer technique or FNAC confirmed AITD. Clinical and laboratory evaluation of 90 of a total of 106 parents and siblings of the 30 institution based cases. METHODS: Clinical evaluation with goiter grading by WHO criteria was done in all. Family history of thyroid disease was inquired for in all. Clinical examination and thyroid antibody status was assessed in 90 family members as stated above. Thyroid antimicrosomal (AMA) and antithyroglobulin (ATG) antibodies were tested by standard hemogglutination kits. Titers of > 1:100 considered +ve for children and >1:400 for adults. Thyroid (ab) could be tested in ten of the ab-ve cases by ECI technique on follow up.Bone age was assessed. Ultrasonographic or TCM 99 scanning of thyroid gland and FNAC were done as indicated. RESULTS: Of the 96 children suspected to have AITD, thyroid antibodies were positive in high titers in 66 (36+30) cases (69%) on initial testing but with more sensitive ECI technique significant antibody titres were detected in 10 more cases (79%) and FNAC confirmed AITD in 2 more subjects (total 78 - initial 66 + 12). F:M ratio was 2.9:1. Sixty one per cent of children were between 6 to 12 years of age; mean age 10.12+/-2.9 years. Seventy seven per cent had hypothyroidism, 10% had thyrotoxicosis and only 13% were euthyroid. Family history of thyroid disease was elicited in 33% of the series. Survey of 90 parents and siblings of the institution based group revealed, euthyroid goiters in 17%, subclinical hypothyroidism in 10% and significant AMA titers in 43% (65% of mothers, 30% siblings and 43% fathers). CONCLUSION: Juvenile AITD is a common cause of acquired thyroid disease in children above 5 years of age with a 3-fold higher prevalence in girls. The manifestations are heterogeneous. Hypothyroidism was most common (77%), euthyroid goiters (13%) and thyrotoxicosis (10%) were less frequent. Familial aggregation was noted in adult family members (33%) with positive thyroid antibodies in 65% of mothers. Sibling affection was less frequent. The familial and genetic implications of AITD are important; diagnosis of AITD in children may also help detect subclinical disease in adult family members.

Persistent hyperinsulinemic hypoglycemia of infancy.

OBJECTIVE: To study the nature and clinical course of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) due to nesidioblastosis. DESIGN: Clinical, laboratory and therapeutic evaluation of infants with this disorder and study the outcome. SETTING: Hospital born neonates and infants referred from other hospitals. SUBJECTS: Thirteen infants from 9 families inclusive of four pairs of siblings referred within few hours of birth to 3 months of age, for seizures. Mean birth weight was 3.68 +/- 0.45 kg. Consanguinity documented in one sporadic and one familial case. METHODS: Clinical and laboratory evaluation by standard biochemical and radioimmunoassay techniques. RESULTS: The mean serum insulin level of 24.2 +/- 12.5 mIU/ml was in the normal range but inappropriately high for the corresponding hypoglycemic blood sugar (23.1 +/- 9.1 mg/dl) value, with an I/G ratio of 1.36 +/- 0.97; as in hyperinsulinemia (normal < 0.4). Investigations excluded other causes of persistent hypoglycemia. A trial of i.v./oral glucose, frequent carbohydrate rich feeds in all, oral diazoxide (10 to 20 mg/kg) in 9/13 cases along with subcutaneous octreotide (20 micrograms/kg QID) in one helped, but pancreatic resection (85 to 90%) was opted for in two (1 familial, 1 sporadic). Six infants including one with pancreatic resection succumbed to hypoglycemia (n = 1) or fulminating infection (n = 3) or brain damage. Of the seven survivors, one familial case with pancreatic resection is brain damaged, and of the six on diazoxide therapy, one is slightly subnormal while one sporadic and three familial cases have done well. One infant was lost to follow up. Diazoxide could be withdrawn in two subjects (1 familial, 1 sporadic) by 8 years of age signifying maturation of islet cell function. CONCLUSION: PHHI appropriately known as 'Islet cell dysmaturation syndrome' is a complex disorder posing problems in diagnosis and therapy. The high familial incidence (77%), with intrafamilial variation in the severity, insulin levels in the normal range but in appropriately high for the blood glucose levels, normal C-peptide levels, with normal I/G ratio (< 0.4) in 4/13 are some of the notable features of this study. Severe recurrent infections in nearly 30%, is an unusual feature in this series and needs an indepth study. The mortality (46%) and morbidity (43%) in survivors is high and calls for greater awareness, early diagnosis and genetic counselling, as this disorder may be familial.

A clinicopathologic profile of adrenocortical tumors.

OBJECTIVE: To study the clinical, biochemical, hormonal, radiological and histopathological profile of adrenocortical tumors in children; to assess the clinicopathological correlations and note the future outcome. DESIGN: Retrospective and prospective study. SETTING: Hospital based; Endocrine Service of our institution and other institution based services. SUBJECTS: 14 children (Females = 11, Males = 3) with adrenocortical tumor, aged 8 months to 13 years (mean age 5.1 +/- 3.42 years), seen over a period of 9 years. RESULTS: Females predominated (F:M = 3.7:1). Majority (64%) had a mixed picture with cushingoid features and virilization, whereas 36% presented only for virilization. Elevated serum cortisol levels with loss of diurnal variation was noted only in those with mixed clinical presentation. Adrenal androgen elevation was noted in majority of cases as virilization was common to all. CT confirmed the diagnosis of tumor, 7 on either side. Thirteen cases were operated. Histopathologic diagnosis was carcinoma in 7 and adenoma in 6 cases. Three of the seven with carcinoma died within 3 months to 2 years but two of these with small tumours (weight 60-65 g and diameter < 6 cm) were well at 2 and 5 years, while as one of the six with a large adenoma had recurrence and metastasis after three years. CONCLUSION: Female preponderance was marked (4 times), 43% of tumors had occurred by 3 years of age and 64% by 6 years. Neither the hormonal parameters nor the histopathology correlated well with the biological behavior and outcome. Prolonged and vigilant follow up is essential.

Disorders of thyroid gland in India.

The profile of thyroid disorders encountered in pediatric and adolescent age groups in India is similar to that seen in most parts of the world except for the prevalence of iodine deficiency disorders in certain endemic regions of this country. Clinical presentation is most commonly for hypothyroidism and goiters and infrequently for hyperthyroidism. Of nearly 800 children referred for thyroid problems, 79% had hypothyroidism (goitrous as well as nongoitrous), 19% had euthyroid goiters and 2% had hyperthyroidism. Hypothyroidism was due to thyroid dysgenesis in 75% (aplasia/hypoplasia--50% and ectopic thyroid gland 25%), thyroiditis in nearly 5% and dyshormonogenes is in 20%. The incidence of congenital hypothyroidism in our experience of screening nearly 40,000 newborns is about 1 in 2,640, which is much higher than the worldwide average of 1 in 3,800. Diagnostic delay in hypothyroidism is common and is related to lack of awareness amongst primary healthy care practitioners and family physicians as well as the cost and availability of laboratory investigations. This delay, compounded with inadequate therapeutic surveillance is responsible for the poor outcome in affected children. High incidence of dyshormonogenesis, inherited as autosomal recessive trait also calls for genetic counselling and routine sibling examination. Our results of family studies on first degree relatives of children with thyroiditis revealed presence of antimicrosomal antibodies in 43% and thyroid disease in 26%. Many etiologic factors cause goiters which may be functionally euthyroid or hypothyroid with almost equal frequency in our series. In nearly 200 schools children surveyed for goiter prevalence, 8% in high socioeconomic groups and about 21% in the low income group, had goiters. Female predominance was marked. However, iodine deficiency was not the sole cause as revealed by dietary survey and urinary iodine estimations. Hyperthyroidism is infrequent, less severe and in our experience responded well to long-term administration of antithyroid drugs. A high index of clinical awareness and education of primary health workers will help a great deal in improving the ultimate outcome in children with thyroid disorders/hypothyroidism.

A multicentric evaluation study of an indigenously prepared cost effective prototype pregnancy test.

A multicentric evaluation of an indigenously developed pregnancy detection kit (named Preglisa) based on urinary human chorionic gonadotropin (hCG) detection was carried out at 12 centres where the outcome of the kit was compared with the existing parameter (e.g., ultrasonography, clinical judgement, serum beta hCG levels) used by the centre for confirmation of the pregnancy. The specificity, sensitivity and accuracy of the kit were 98.05, 98.7 and 98.69 per cent (n = 382) when results of Preglisa were compared with those of non-immunological tests. When compared with commercially available kits, sensitivity was 97.9 per cent, specificity was 97.2 per cent and accuracy was 97.94 per cent (n = 155). The kit is cost effective with a sensitivity of 300 mlU/ml and is recommended for detecting pregnancy 35 days after the last menstrual period thus fulfilling the general requirement in the Indian situation.

Neonatal screening for congenital hypothyroidism using the filter paper thyroxine technique.

A total of 25,244 full term consecutive newborns were screened for hypothyroidism at 24 to 96 h of birth using the filter paper technique for thyroxine. The screening protocol based on our pilot study considered filter paper thyroxine (FP-T4) values of 51 to 80 ng/ml (-1 SD) as borderline and < 50 ng/ml (-2 SD) as high risk for congenital hypothyroidism. FP-T4 and/or serum T4 and TSH were reestimated in all neonates with FP-T4 < 80 ng/ml. A total of 4775 (18.9%) newborns (FP-T4, 51 to 80 ng/ml in 4435 and < 50 ng/ml in 340) needed the recall; 2237 (50.4%) with FP-T4 51 to 80 ng/ml recalled by letters and 283 (83.3%) of the 340 subjects with FP-T4 < 50 ng/ml recalled by home visit, responded by 6 wk of age. Congenital hypothyroidism was confirmed in 6 newborns. FP-T4 in one persisted at 55 ng/ml on follow up and in the remainder both initial and repeat values were < 50 ng/ml. Follow up serum T4 values were subnormal (7.8-50.2 ng/ml) and serum TSH elevated (80-1233 IU/ml). Technetium thyroid scan showed agenesis in 3, ectopia in 2 and normal gland with probable dyshormonogenesis in one. Three other newborns (FP-T4 93 to 143 ng/ml) escaped primary detection and were referred later for congenital hypothyroidism. The incidence of congenital hypothyroidism by primary screening was 1:4207 (6 of 25,244) but with these 3 missed cases, probably 1:2804. Congenital hypothyroidism was reconfirmed in all 9 infants between the ages of 2 1/2 to 4 yr.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothalamic hamartomas and precocious puberty.

Ten children, five boys and five girls with true precocious puberty at an early age were found to have hypothalamic hamartomas on brain imaging. Very early onset of puberty, varying from a few weeks to three years of age, and rapid progression were characteristic. Accelerated growth velocity and markedly advanced bone age were evident in all. Gonadotropin and gonadal hormone levels were elevated above the prepubertal range. Six children had associated developmental delay or hyperactivity.