A case of novel mutation in ANOS1 (KAL1) gene and review of Kallmann syndrome.

Summary: Kallmann syndrome (KS) is a genetically heterogeneous condition characterized by hypogonadotropic hypogonadism with coexisting anosmia or hyposmia along with potential other phenotypic abnormalities depending on the specific genetic mutation involved. Several genetic mutations have been described to cause KS. The ANOS1 (KAL1) gene is responsible for 8% of mutations causing KS. A 17-year-old male presented to our clinic with delayed puberty and hyposmia, along with a family history suggestive of hypogonadism in his maternal uncle. Genetic testing for KS revealed complete exon 3 deletion in the ANOS1 gene. To the best of our knowledge, this specific mutation has not been previously described in the literature. Learning points: Missense and frameshift mutations in the KAL1 or ANOS1 gene located in the X chromosome are responsible for 8% of all known genetic mutations of Kallmann syndrome. Exon 3 deletion is one of the ANOS1 gene is a novel mutation, not reported before. Targeted gene sequencing for hypogonadotropic hypogonadism can be employed based on the phenotypic presentation.

Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic.

PURPOSE: Congenital hypopituitarism usually occurs sporadically. In most patients, the etiology remains unknown. METHODS: We studied 13 children with sporadic congenital hypopituitarism. Children with non-endocrine, non-familial idiopathic short stature (NFSS) (n = 19) served as a control group. Exome sequencing was performed in probands and both unaffected parents. A burden testing approach was used to compare the number of candidate variants in the two groups. RESULTS: First, we assessed the frequency of rare, predicted-pathogenic variants in 42 genes previously reported to be associated with pituitary gland development. The average number of variants per individual was greater in probands with congenital hypopituitarism than those with NFSS (1.1 vs. 0.21, mean variants/proband, P = 0.03). The number of probands with at least 1 variant in a pituitary-associated gene was greater in congenital hypopituitarism than in NFSS (62% vs. 21%, P = 0.03). Second, we assessed the frequency of rare, predicted-pathogenic variants in the exome (to capture undiscovered causes) that were inherited in a fashion that could explain the sporadic occurrence of the proband's condition with a monogenic etiology (de novo mutation, autosomal recessive, or X-linked recessive) with complete penetrance. There were fewer monogenic candidates in the probands with congenital hypopituitarism than those with NFSS (1.3 vs. 2.5 candidate variants/proband, P = 0.024). We did not find any candidate variants (0 of 13 probands) in genes previously reported to explain the phenotype in congenital hypopituitarism, unlike NFSS (8 of 19 probands, P = 0.01). CONCLUSION: Our findings provide evidence that the etiology of sporadic congenital hypopituitarism has a major genetic component but may be infrequently monogenic with full penetrance, suggesting a more complex etiology.

Severe hyperthyroidism without symptoms due to nonthyroidal illness in a child with acute hepatitis: case report and literature review.

While liver enzyme changes are frequently reported in hyperthyroidism, liver dysfunction itself can lead to alterations in thyroid hormone metabolism. However, the exact relationship between hyperthyroidism and liver dysfunction is unclear. We report an 11-year-old boy presenting with acute hepatitis of unknown etiology, who was incidentally found to have asymptomatic biochemical hyperthyroidism. Despite significant total and free T4 elevation, clinical evidence of thyrotoxicosis was absent. Thyroid I-123 uptake was also reduced. Additional testing revealed slight T3 elevation and significant rT3 elevation. Graves' and Hashimoto's thyroiditis testing was negative. We hypothesize that the biochemical hyperthyroidism was due to transient thyroiditis. Although an etiology for the boy's hepatitis was never determined, and an undiagnosed infectious etiology causing subacute thyroiditis was considered, subsequent testing showing positive thyroid peroxidase antibodies, suggesting autoimmune Hashimoto's thyroiditis as the likely cause of the hyperthyroidism. We believe, furthermore, that the absence of symptoms was the result of concurrent nonthyroidal illness resulting in the biochemical findings of slight T3 elevation and significant rT3 increase despite significant T4 elevation.

Diagnosis and management of hypopituitarism.

PURPOSE OF REVIEW: This review summarizes pituitary function, and the clinical presentation and treatment of hypopituitarism. RECENT FINDINGS: Updates in the field include new guidelines and meta-analyses on the diagnosis and treatment of select hormone deficiencies, novel treatment options, and advances in next generation sequencing technology. SUMMARY: Hypopituitarism is defined as partial or complete loss of a single or multiple pituitary hormones. The clinical presentation of hypopituitarism varies depending on the number and severity of hormone deficiencies. Treatment involves the physiologic replacement of the individual end-organ hormone deficiencies and requires close lifelong monitoring.

Veganism as a cause of iodine deficient hypothyroidism.

BACKGROUND: Iodine deficiency is the most common cause of acquired hypothyroidism worldwide. Although uncommon in the Western world, the incidence of iodine deficiency may be rising due to the increased use of restrictive diets. CASE PRESENTATION: We present a 23-month-old boy diagnosed with iodine deficiency hypothyroidism, induced by a vegan diet. CONCLUSIONS: This case highlights the risk for iodine deficiency in children on a vegan diet after discontinuation of breast/formula feeding that could lead to acquired hypothyroidism.

Grid-immunoblotting.

Grid-immunoblotting is a fast, simple, and efficient method for simultaneously testing multiple allergens utilizing small amount of antibody.

Grid-immunoblotting.

Grid-Immunoblotting is a fast, simple, and efficient method for simultaneously testing multiple allergens utilizing small amount of antibody.

The neuropsychology of cocaine addiction: recent cocaine use masks impairment.

Individuals with current cocaine use disorders (CUD) form a heterogeneous group, making sensitive neuropsychological (NP) comparisons with healthy individuals difficult. The current study examined the effects on NP functioning of four factors that commonly vary among CUD: urine status for cocaine (positive vs negative on study day), cigarette smoking, alcohol consumption, and dysphoria. Sixty-four cocaine abusers were matched to healthy comparison subjects on gender and race; the groups also did not differ in measures of general intellectual functioning. All subjects were administered an extensive NP battery measuring attention, executive function, memory, facial and emotion recognition, and motor function. Compared with healthy control subjects, CUD exhibited performance deficits on tasks of attention, executive function, and verbal memory (within one standard deviation of controls). Although CUD with positive urine status, who had higher frequency and more recent cocaine use, reported greater symptoms of dysphoria, these cognitive deficits were most pronounced in the CUD with negative urine status. Cigarette smoking, frequency of alcohol consumption, and dysphoria did not alter these results. The current findings replicate a previously reported statistically significant, but relatively mild NP impairment in CUD as compared with matched healthy control individuals and further suggest that frequent/recent cocaine use [corrected] may mask underlying cognitive (but not mood) disturbances. These results call for development of pharmacological agents targeted to enhance cognition, without negatively impacting mood in individuals addicted to cocaine.