Congenital Hypothyroidism with Thyroid in situ: A Case Report with NKX2-1 and DUOX2 Hypomorphic Variants.

INTRODUCTION: NK2 homeobox 1 (NKX2-1) encodes a transcription factor, NKX2-1, that is expressed in the thyroid gland, lung, and brain. Dual oxidase 2 (DUOX2) encodes an enzyme which generates hydrogen peroxide and is involved in the thyroid hormone synthesis. Cases of congenital hypothyroidism (CH) with dyshormonogenesis showing two or more genetic variants are increasingly reported. We describe the first case of transient dyshormonogenesis who had experimentally verified a loss-of-function NKX2-1 variant and DUOX2 variants. CASE PRESENTATION: The proband was a 15-year-old female patient with CH who was diagnosed in the frame of newborn screening for CH. She had a mildly elevated serum TSH level (14.56 mU/L), a low free thyroxine level (0.87 ng/dL), and a high thyroglobulin (Tg) level (>800 ng/mL). Ultrasonography revealed goiter. She was followed clinically without levothyroxine treatment and showed normal growth and development. She had slightly high Tg levels throughout the clinical course. Next-generation sequencing-based genetic analysis revealed that the patient was heterozygous for an NKX2-1 variant (p.Ile228Ser), a nonsense DUOX2 variant (p.[Lys530*;His678Arg]), and a functional DUOX2 polymorphism (p.His678Arg). NKX2-1 p.Ile228Ser showed about 50% reduced residual activity on the Tg promoter. CONCLUSION: A partial loss-of-function NKX2-1 variant with a monoallelic nonsense DUOX2 variant and a DUOX2 functional polymorphism can cause transient CH with high serum Tg levels.

Acute Adrenal Insufficiency Caused by Mental Stress in a Patient With Adrenocorticotropic Hormone Deficiency.

In patients with chronic adrenal insufficiency, physical stress increases the requirement for glucocorticoid therapy. Although mental stress may cause acute adrenal insufficiency, it is debatable how patients should be treated when experiencing mental stress. Here, we report the case of a female patient with septo-optic dysplasia who had been treated for adrenocorticotropic hormone deficiency since infancy. After her grandfather died when she was 17 years old, she complained of nausea and stomach pain. Her symptoms failed to improve despite treatment with stress doses of oral hydrocortisone and self-administered glucagon injection. Her general condition improved after she began receiving continuous hydrocortisone and glucose infusions. Glucocorticoid stress doses should be given early if a patient is likely to experience mental stress.