The word adrenocorticotropin (ACTH) resistance syndrome can be used to get a combined band of rare inherited disorders, which present with primary adrenal insufficiency during childhood. of the nonconsanguineous relationship and got an young Acetazolamide and elder sibling, who didn’t have any identical issues. On questioning, the mom gave a past history of absent tear production while crying in the kid. There is no past background of problems in deglutition to solids or fluids, retrosternal chest discomfort, or regurgitation of undigested meals particles. He refused background of orthostatic dizziness, dryness of pores and skin, problems in dark version, or any additional autonomic disturbances. Exam revealed a, average constructed male having a elevation of 121 cm (at 10th centile in K.N. Agarwal’s development charts with focus on elevation also in the same centile), a pounds of 22 kg (at 25th centile in K.N. Agarwal’s development graphs) and body mass index of 15.0 kg/m2. His blood circulation pressure Acetazolamide was 90/70 mm Hg without postural drop. He previously generalized hyperpigmentation relating to the knuckles, palmar crease, nail, extensor areas of extremities, and mucosa from the tongue. Intimate maturity ranking was Tanner stage III with testicular level of 10 mL bilaterally. The rest of the systemic and general examination including detailed neurological examination was unremarkable. Laboratory investigations including hemogram, renal function tests, serum electrolytes, liver function tests, and fasting plasma glucose were within normal limits. Bone age (Greulich and Pyle Atlas) was consistent with chronological age. Endocrine evaluation [Table 1] revealed 8 am serum cortisol 1.53 g/dL (normal range: 6.2C19.4 g/dL), plasma ACTH 1538 pg/mL (normal range: 7.2-63.3 pg/mL), serum T4 9.5 g/dL (normal range: 5.1C14.1 g/dL), and serum thyroid-stimulating hormone (TSH) 8.4 IU/mL (normal range: 0.27-4.2 IU/ml) (all hormones measured on an autoanalyzer; Roche Elecsys 2010, Roche Diagnostics, Germany, using electrochemiluminescence immunoassay). Basal plasma aldosterone and renin concentration were found to be normal at 25.14 ng/dL (normal range: 2.2C35.3 ng/dL) and 8.19 mU/L (normal range: 4.4C46.1 mU/L), respectively. Further work-up included ultrasonography of the abdomen, which revealed bilateral atrophic adrenals. Schirmer’s test response was 5 mm in both eyes, suggestive of severe dry eyes. At this stage, a possibility of ACTH resistance due to triple A syndrome was entertained and the patient was investigated further for possible achalasia cardia. While a barium swallow study was normal, gastroenterologist found increased resistance at the lower end of esophagus on upper gastrointestinal endoscopy procedure, suggestive of achalasia cardia. Esophageal manometry revealed high basal lower esophageal sphincter (LES) pressure with incomplete LES relaxation on wet swallows and absent esophageal peristalsis, with few spastic peristaltic fragments, confirming the diagnosis of achalasia cardia. He was started on physiological glucocorticoid supplementation with education on stress dosing. The treatment regimen comprised prednisolone twice daily initially, which was changed to dexamethasone once daily after epiphyseal fusion to improve the treatment compliance. Hyperpigmentation and anorexia gradually improved with treatment. TSH normalized on serial treatment with steroids without thyroxine supplementation, suggesting subclinical hypothyroidism due to glucocorticoid deficiency. For dry eyes, lubricant eye drops were prescribed, while he was followed up conservatively for achalasia, which has been asymptomatic till now. The child has been following up with us regularly and achieved a final height of 169 cm (as per the expected genetic potential). DISCUSSION We have described three cases with primary adrenal insufficiency due to ACTH resistance syndrome. All the three cases had isolated primary glucocorticoid deficiency with preservation of reninCangiotensinCaldosterone axis. While cases 1 and 2 were siblings who presented with features of FGD, case 3 presented with alacrima along with primary glucocorticoid deficiency and was diagnosed as triple A syndrome. FGD was referred to by Shepard gene primarily, situated on chromosome 18q11, encodes a 297-amino acidity G-protein-coupled receptor. A lot more than 30 mutations have already been referred to in gene, most Acetazolamide that are homozygous substance or missense heterozygous mutations. No more than 25% of FGD is due to mutations in the gene. Recently, mutations have already been within gene also, which is necessary for MC2R expression using cell types, suggesting that MRAP is important in control, trafficking, or function from the MC2R. mutations take into account 15%C20% of most FGD instances. Nevertheless, no mutations are recognized in 55%C60% of individuals with FGD. Our individuals (instances 1 and 2) also didn’t display any mutation in or gene. It’s important to differentiate FGD from other notable causes of major hypoadrenalism in kids as alternative of mineralocorticoid is not needed in FGD, while mineralocorticoid alternative is vital and life-saving in additional circumstances of primary hypoadrenalism generally. Triple A symptoms was first referred to by Allgrove in 1978. The disorder is inherited within an autosomal recessive design and is due to mutation in gene situated on 12q13, which rules for the 546 amino Nr4a1 acidity nuclear pore complex protein ALADIN..