Endocrine Abstracts

Introduction

Triple-A syndrome (AS) is a rare autosomal recessive disorder, defined by the coexistence of primary adrenal insufficiency (PAI), alacrimia and achalasia cardia. The association to other endocrine has so far not been reported in the literature. Herein, we describe the coexistence of AS and congenital hypogonadotropic hypogonadism in two cases.

Case presentation 1

An 18-year-old patient, child of a consanguineous family, was admitted for short stature, delayed puberty and gynecomastia. He had a medical history of triple AS: alacrimia, PAI was revealed at the age of 5 by recurrent convulsive seizures secondary to hypoglycemia, achalasia cardia diagnosed one year later and treated by Heller myotomy. Examination showed obesity, a height of 142 cm; his stature age = 11 years while his bone age = 13 years. Tanner stage G1P1A1. Growth hormone (GH) secretion was normal after stimulation. The testosterone serum level was low (0.14 nmol/l), basal LH level = 0.18 mU/ml and basal FSH level = 1.6 mU/ml. The positive response to the GnRH test indicates a hypothalamic origin of the gonadotropin deficiency. Hypothalamic pituitary MRI was normal. The karyotype was normal. A homozygous splice-donor site mutation (IVS14 + 1G b A) was found in the AAAS gene.

Case presentation 2

A 5-years-old male with a medical history of alacrimia, first consulted at the age of 5 for dysphagia, regurgitations and growth delay. Esophageal manometry confirmed the diagnosis of achalasia. And the low levels of serum cortisol at 28 nmol/l confirmed the diagnosis of PAI. A replacement therapy with hydrocortisone was started, and the patient underwent a myotomy at the age of 6. The patient’s younger sister was also being treated in the same pediatric hospital for AS. He was referred to our department at the age of 23 for acute adrenal insufficiency. Examination showed a stature delay (height = 141 cm) and a normal development of secondary sex characteristics. His bone age corresponded to that of 14 years. Further investigation revealed a GH deficiency (L-Dopa test), and a hypogonadotropic hypogonadism (testosterone = 1.26 ng/ml, FSH = 3.3 mU/ml and LH = 3.97 mU/ml) resulting in osteoporosis. Pituitary MRI showed no abnormalities. Mutation screening is not yet performed.

Conclusions

To our knowledge, the association of AS to Hypogonadotropic Hypogonadism was never reported outside of our department. In absence of achalasia and alacrimia, PAI and hypogonadotropic hypogonadism in a male would point towards X-linked adrenal hypoplasia congenita. Nevertheless, AS diagnosis in these two cases was evident.