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  • Molecular genetic analysis x
  • Growth hormone deficiency (childhood onset) x
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Open access

Susan Ahern, Mark Daniels and Amrit Bhangoo

Summary

In this case report, we present a novel mutation in Lim-homeodomain (LIM-HD) transcription factor, LHX3, manifesting as combined pituitary hormone deficiency (CPHD). This female patient was originally diagnosed in Egypt during infancy with Diamond Blackfan Anemia (DBA) requiring several blood transfusions. Around 10 months of age, she was diagnosed and treated for central hypothyroidism. It was not until she came to the United States around two-and-a-half years of age that she was diagnosed and treated for growth hormone deficiency. Her response to growth hormone replacement on linear growth and muscle tone were impressive. She still suffers from severe global development delay likely due to delay in treatment of congenital central hypothyroidism followed by poor access to reliable thyroid medications. Her diagnosis of DBA was not confirmed after genetic testing in the United States and her hemoglobin normalized with hormone replacement therapies. We will review the patient’s clinical course as well as a review of LHX3 mutations and the associated phenotype.

Learning points:

  • Describe an unusual presentation of undertreated pituitary hormone deficiencies in early life

  • Combined pituitary hormone deficiency due to a novel mutation in pituitary transcription factor, LHX3

  • Describe the clinical phenotype of combined pituitary hormone deficiency due to LHX3 mutations

Open access

Jordan Yardain Amar, Kimberly Borden, Elizabeth Watson and Talin Arslanian

Summary

Isolated Growth Hormone Deficiency (IGHD) is a rare cause of short stature, treated with the standard regimen of subcutaneous synthetic growth hormone (GH). Patients typically achieve a maximum height velocity in the first year of treatment, which then tapers shortly after treatment is stopped. We report a case of a 9-year-old male who presented with short stature (<3rd percentile for age and race). Basal hormone levels showed undetectable serum IGF1. Skeletal wrist age was consistent with chronologic age. Cranial MRI revealed no masses or lesions. Provocative arginine-GH stimulation testing demonstrated a peak GH level of 1.4 ng/mL. Confirmatory genetic testing revealed a rare autosomal recessive single-nucleotide polymorphism (SNP) with mutational frequency of 2%. GH supplementation was started and pursued for 2 years, producing dramatically increased height velocity. This velocity persisted linearly through adolescence, several years after treatment had been discontinued. Final adult height was >95th percentile for age and race. In conclusion, this is a case of primary hypopituitarism with differential diagnosis of IGHD vs Idiopathic Short Stature vs Constitutional Growth Delay. This case supports two objectives: Firstly, it highlights the importance of confirmatory genetic testing in patients with suspected, though diagnostically uncertain, IGHD. Secondly, it demonstrates a novel secondary growth pattern with implications for better understanding the tremendous variability of GH treatment response.

Learning points:

  • GHD is a common cause of growth retardation, and IGHD is a specific subtype of GHD in which patients present solely with short stature.

  • The standard treatment for IGHD is subcutaneous synthetic GH until mid-parental height is reached, with peak height velocity attained in the 1st year of treatment in the vast majority of patients.

  • Genetic testing should be strongly considered in cases of diagnostic uncertainty prior to initiating treatment.

  • Future investigations of GH treatment response that stratify by gene and specific mutation will help guide treatment decisions.

  • Response to treatment in patients with IGHD is variable, with some patients demonstrating little to no response, while others are ‘super-responders.’