Allgrove syndrome: case report of 7 years old boy from Bahawalpur.

Allgrove syndrome is a rare autosomal recessive syndrome of unknown prevalence. The first case of Allgrove syndrome was reported in 1978 by Allgrove. It is characterized by triad of achalasia, alacrima and adrenal hypoplasia. There are also associated autonomic and neurological manifestations. We report the case of a 7 years old boy being treated for achalasia cardia, presented with fits and altered sensorium which on further investigations was found to be due to adrenal insensitivity (Raised ACTH level, low Cortisol level, and normal Aldosterone and Renin ratio). He also had undiagnosed alacrima since birth, mild degree of hearing loss and autonomic instability in the form of episodic hypertension.

Central hypoadrenocorticism associated with Rathke's cleft cyst.

Rathke's cleft cysts (RCCs) are non-neoplastic, sellar or suprasellar epithelium-lined cysts originating from Rathke's pouch in the pituitary gland. Patients with RCCs are usually asymptomatic, but some have only been identified when symptoms manifested in middle age. The characteristics of these patients during childhood or adolescence remains unknown. We describe an 18-year-old girl who had occasionally suffered from malicious fatigue in the morning since her early teens. Brain magnetic resonance imaging (MRI) revealed T1 hyperintense/T2 hypointense signals between the anterior and posterior pituitary glands, indicating the presence of RCC. Based on an authentic endocrinological evaluation, her adrenal function seemed normal; nevertheless, her serum cortisol level strangely dropped around noon. Furthermore, daily supplementation of oral hydrocortisone bizarrely suppressed ACTH secretion to below the detection range in the morning. These data appeared compatible with the presence of central adrenal dysfunction. We also review the literature for previously reported cases. In conclusion, the symptoms and endocrinological data for dysfunction of the hypothalamic pituitary system might be non-specific and vary among patients, especially in teenagers. Brain MRI and daily cortisol profiling in blood are key to obtaining a diagnosis of an impaired hypothalamic adrenal function due to RCC.

Allgrove syndrome with prominent neurological symptoms. Case Report.

We report a young woman with the clinical picture of Allgrove syndrome in whom neurological symptoms are prominent. It usually presents in the first decade of life with a deficiency of tears, recurrent vomiting and dysphagia due to achalasia, severe hypoglycemic seizures and shock due to adrenal insufficiency. Neurological symptoms such as hyperreflexia, dysarthria, hypernasal speech, ataxia, sensory impairment, muscle weakness, and mental retardation are extremely slow to develop and manifest at a later age. Diagnosis was based on clinical presentation and laboratory findings. She is the first patient from the Czech Republic with genetic confirmation of Allgrove syndrome. This patient is one of about 100 cases described in the literature and one of the few patients with all the main typical clinical features.

Surgical treatment of infantile achalasia: a case report and literature review.

Allgrove syndrome is a rare genetic disorder typically manifested by alacrima, achalasia, and adrenal insufficiency, and is one of the rare causes of achalasia in infants. While the gold standard for achalasia treatment in adults is an esophageal myotomy with fundoplication, a standard treatment for infantile achalasia remains undetermined due to the low number of reported cases and rarity of the disease in this age group. We report a 7.7 kg infant with achalasia secondary to Allgrove syndrome who was successfully treated by Heller myotomy and simultaneous Toupet fundoplication. This case represents one of the smallest patients to ever be treated for achalasia and highlights the role that primary surgical therapy may have for the infantile variant of the disease.

New insights into X-linked adrenal hypoplasia congenita from a novel splice-site variant of NR0B1 and adrenal CT images.

BACKGROUND: X-linked adrenal hypoplasia congenita (AHC) is a rare disorder, often manifesting as primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), and caused by variants of NR0B1, most of which are frame-shifting variants, and few splice-site variants. METHODS AND RESULTS: Here, a novel splice-site variant of NR0B1 (NM_000475.4), c.1169-2A>T (patient 1), and a stop-loss variant of NR0B1 c.1411T>C (patient 2) are described in this study. We perform minigene assays for the splice-site variant (c.1169-2A>T) and determine that the variant causes exon 2 skipping. Moreover, the defect of NR0B1 protein may bring about the severe phenotype of the patient. Through 8 years of follow-up, we compare the CT images from 8 years ago with the latest image, and observe the CT image change of adrenal in patient 2 (from the increased thickness of adrenal to adrenal atrophy). CONCLUSION: X-linked adrenal hypoplasia congenita is produced by variants of NR0B1. We report a case that presents a novel splice-site variant, which has been verified that it could lead to the exon 2 skipping in the RNA splicing progress. Moreover, we report the adrenal CT image change of patient 2, which has never been referred to before, and expand the spectrum of X-linked AHC characteristics.

Characterization of clinicopathologic and abdominal ultrasound findings in dogs with glucocorticoid deficient hypoadrenocorticism.

BACKGROUND: Clinical findings of glucocorticoid-deficient hypoadrenocorticism (GDH) can overlap with other diseases, presenting a diagnostic challenge. OBJECTIVES: Describe clinicopathologic and ultrasonographic features of dogs with GDH and those suspected of having GDH that had the disease ruled out. ANIMALS: Six hundred twenty-three dogs. METHODS: Records from dogs with suspected GDH between 2003 and 2018 were reviewed. Dogs with hyperkalemia or hyponatremia were excluded. Dogs were categorized as controls when the resting serum cortisol or post-ACTH cortisol concentration were > 2 µg/dL. Clinicopathologic and ultrasonographic features were compared between groups. The optimal cut-point, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated for individual features used to detect GDH. RESULTS: Dogs were categorized as GDH (n = 29) or controls (n = 594). Lymphocyte count (>1750 cells/L; sensitivity, 96.6%; 95% confidence interval [CI], 82.8%-99.8%; specificity, 60.3%; 95% CI, 56.3%-64.1%; AUC, 0.828; 95% CI, 0.762-0.894) and albumin/globulin ratio (<1.081; sensitivity, 86.2%; 95% CI, 69.4%-94.5%; specificity, 78.8%; 95% CI, 75.3%-81.9%; AUC, 0.886; 95% CI, 0.827-0.944) had the highest discriminatory power between groups. Left adrenal gland width <0.39 cm was 80% (95% CI, 58.4%-91.9%) sensitive and 82.4% (95% CI, 74.2-88.4) specific for GDH. Serum cobalamin concentrations and ultrasonographic abnormalities of the GI tract were not different between groups. CONCLUSION AND CLINICAL IMPORTANCE: No single variable could be used to confidently rule out GDH and obviate the need for cortisol testing in dogs with a clinical presentation consistent with GDH.

A Case report: Co-occurrence of IMAGe syndrome and Rhabdomyosarcoma.

IMAGe syndrome is a rare congenital disorder, presenting with intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital anomalies (in males). So far only 17 individuals have been diagnosed molecularly with IMAGe syndrome, this patient is the first case of an individual diagnosed with IMAGe and concurrent rhabdomyosarcoma. The patient was born at 30 weeks' gestation and received treatment for hyponatremia and hyperkalemia. At 4 9/12 years of age the patient showed a painless, non-mobile mass on the left thigh. In the biopsy performed a sarcoma weave with solid, nest-like growth, with characteristics of rhabdomyosarcoma was identified. The family history and physical examination indicated IMAGe syndrome so genetic testing was requested. A whole exome sequencing procedure with use of SureSelectXT Human ALL Exon V7, confirmed a single nucleotide variant NM_000076.2(CDKN1C):c.820G>A (p.Asp274Asn); identifying a missense mutation in the imprinted gene CDKN1C associated with IMAGe syndrome. Although tumours associated with CDKN1C are rare, deregulation of imprinted genes is increasingly being recognised as a mechanism of tumorigenesis in cancer; chromosomal region 11p15.5 contains a cluster of imprinted genes. This same region is the most consistent site of allele loss in rhabdomyosarcoma and is the same region altered in both IMAGe and Beckwith-Wiedemann syndrome. Molecular studies have found genetic changes in the 11p15 region in a variety of embryonal tumours like Wilms tumours which are commonly developed in Beckwith-Wiedemann syndrome and embryonal rhabdomyosarcoma. Through this case we aim to present the possibility of oncogenesis in patients with IMAGe syndrome, specifically rhabdomyosarcoma.

Surgery versus conservative care for Rathke's cleft cyst.

BACKGROUND: Rathke's cleft cysts are benign cystic lesions of the sellar region, which may cause headache, pituitary deficiencies and visual disturbances from mass effect. Their management is not standardized yet. This study is about establishing a consensus for medical care of RCC. MATERIAL AND METHODS: We performed a retrospective observational study of all patients that were diagnosed or followed for RCC between 2008 and 2018 (11 years), in the neurosurgical and the adult endocrine departments of our institution. The study's average time length of follow-up is 72.9 months (from 2 to 385 months). RESULTS: The 57 included patients were divided into 2 groups: group A, which included 39 patients that were conservatively managed and group B, which included 18 surgically treated patients. Group A showed either an improvement or a spontaneous resolution of headaches in 56.1% of the cases (P<0.01); a resolution of hyperprolactinemia in 70% of the cases (P=0.21); and of hypogonadism, ACTH deficiency, growth hormone deficiency in 100% of the cases. There was no spontaneous improvement of visual disturbances (P<0.01) or diabetes insipidus (P=0.29) during follow-up. Regarding group B, surgery allowed improvement or complete resolution of headaches in 60% of the cases; visual troubles in 100% of the cases (P<0.01); and hyperprolactinemia in 100% of the cases. Pituitary deficiencies were not improved by surgery. CONCLUSIONS: This study offers guidance in decision-making regarding the management of RCC patients. Surgery is particularly suitable for treating visual disturbances caused by RCC. Regular follow-up is more appropriate than surgery concerning headaches, hyperprolactinemia, endocrine disruptions and diabetes insipidus.

Postnatal changes in adrenal size in very low-birth-weight infants: sonographic evaluation for the prediction of late-onset glucocorticoid-responsive circulatory collapse.

We investigated the postnatal pattern of changes in adrenal size in very low-birth-weight (VLBW) infants and its relation to late-onset glucocorticoid-responsive circulatory collapse (LGCC) that may be associated with adrenal insufficiency. In 36 VLBW infants born at <33 weeks' gestation, ultrasound examinations of postnatal changes in adrenal size during the first 3 weeks of life were performed. VLBW infants were classified into three groups: group A (N = 6), the actual adrenal area was greater than or equal to the predicted value at birth and unchanged at 3 weeks; group B (N = 24), the actual adrenal area was greater than or equal to the predicted value and decreased at 3 weeks; and group C (N = 6), the actual adrenal area was less than the predicted value and unchanged at 3 weeks. Five infants developed LGCC, and all five were in group A. These observations suggest that the life of the adrenal fetal zone might be extended beyond 3 weeks after birth in some VLBW infants and that prolonged fetal zone activity might correlate with LGCC. On the other hand, adrenal maturation might have already occurred at birth in some VLBW infants. Sonographic evaluation of adrenal size may enable prediction of subsequent LGCC in VLBW infants.

Prolonged Adrenal Insufficiency After the Discontinuation of Mitotane Therapy.

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare neoplasm characterized by a high risk of recurrence after radical resection. The role of adjuvant systemic therapy in radically resected patients is unclear. Mitotane, a steroidogenesis inhibitor, is the only drug approved for the systemic treatment of advanced ACC. In 2007, a retrospective case-control study provided the evidence that mitotane, administered for two years after successful surgery, could prolong recurrence-free survival. Adrenal insufficiency (AI), which occurs in almost all patients during the first 12 months of treatment, is an expected side effect of mitotane and requires steroid replacement therapy. Due to its long halflife, mitotane-induced AI persists several months after treatment discontinuation and is managed by cautious tapering of glucocorticoid replacement therapy. RESULTS: We report a case of symptomatic AI diagnosed after a severe allergic reaction occurring three years after the discontinuation of adjuvant mitotane therapy. CONCLUSION: The case suggests that mitotane-induced AI should be monitored for a long time to asses full recovery of adrenal function, in order to prevent adrenal crises.

Bilateral adrenal histoplasmosis presenting as adrenal insufficiency in an immunocompetent host in the Philippines.

Disseminated histoplasmosis, with the adrenal glands as being the only site of demonstrable disease in an immunocompetent adult, is a rare infection leading to adrenal insufficiency. This disease carries high mortality when unrecognised. We describe the first reported case of adrenal histoplasmosis in the Philippines in a 72-year-old immunocompetent, Filipino man who presented with a 3-month history of intermittent flank pain, weight loss and generalised weakness. His imaging demonstrated bilateral adrenal masses on ultrasonography and contrast-enhanced CT scan. The initial impression was adrenal cancer, however, fine-needle aspiration cytology revealed the presence of yeast cells and blood culture grew Histoplasma capsulatum The diagnosis of the case represents a diagnostic challenge in immunocompetent individuals because they manifest with non-specific symptoms. A heightened suspicion is therefore needed to prevent significant morbidity and mortality.

[Analysis of causes contributing to inefficiency of roentgenoendovascular destruction of adrenal glands in hypertensive patients].

The study was aimed at bettering therapeutic outcomes for patients suffering from adrenal-aetiology arterial hypertension, with the objective deemed attainable at the expense of revealing and removing the underlying causes potentially contributing to unfavourable results obtained after roentgenoendovascular ablation of the adrenal glands. We retrospectively examined the medical records of 49 patients having undergone hospital treatment within the time frame from 1992 to 2007 for recurrent arterial hypertension poorly controlled by previously endured roentgenoendovascular (REV) interventions. The identified causes contributing heavily to poor clinical outcomes obtained after the REV-ablation procedures appeared to have been as follows: renal parenchymatous diseases in 20 patients having a long history of arterial hypertension with evidence ofnephroangiosclerosis; insufficient devitalisation of the adrenal glands in a further 19 patients; a pheochromocytoma of the right adrenal gland in only one instance; and newly onset renovascular hypertension in the remaining nine subjects. It was determined that poor therapeutic outcomes had primarily been caused by overestimating the indications for performing REV ablation of the adrenal glands, being seemingly wanton as a corrective measure to have been taken in the presence of inflammatory diseases of the renal parenchyma and secondary hyperplasia of the adrenal gland, with the second-in-order contributory cause appearing to be insufficient devitalisation of the adrenal glands afflicted by hyperplasia and/or aldosteroma. The development of renal artery stenosis in the remote period after REV interventions may also be responsible for a relapse of arterial hypertension, which is quite often the case.

Adrenal haemorrhage with cholestasis and adrenal crisis in a newborn of a diabetic mother.

The large hyperaemic foetal adrenal gland is vulnerable to vascular damage. This may occur in the neonatal period as a consequence of difficult labour, or its aetiology may not be apparent. The spectrum of presentation is considerable, ranging from asymptomatic to severe life-threatening intra-abdominal haemorrhage. The presentation of adrenal insufficiency may be delayed but the regenerative capacity of the adrenal is great, and most adrenal haemorrhage is not associated with significantly impaired function. Some reports showed that cholestatic hepatopathy with congenital hypopituitarism reversed by hydrocortisone treatment is considered in the context of the endocrine syndrome, probably as a consequence of the adrenal failure. We describe a case of bilateral adrenal haemorrhage with hepatitis syndrome and persistent hypoglycaemia in a newborn male with striking features of neonatal cholestasis and adrenal crisis.