Clinical Profile of Addison's Disease in a Tertiary Care Institute, Southern India - The Changing Landscape.

Aims and Objectives: Clinical, biochemical, and radiological profiles of Addison's disease and to assess the various etiological spectrum of primary adrenal insufficiency (PAI) in adults. Materials and Methods: A retrospective cohort study was carried out in the Department of Endocrinology, Madurai Medical College, Madurai between January 2014 and January 2021 over a 7-year period. Inclusion Criteria: All the patients with clinical symptoms and or signs of suspected PAI, such as hyperpigmentation, weight loss, persistent nausea or vomiting, fatigue, and hypotension, were recruited. All suspected cases underwent measurement of 8-AM plasma ACTH and cortisol levels. In possible cases and equivocal cortisol levels, patients underwent Co-syntropin/ACTH stimulation test. To know the underlying etiology of PAI, 21-hydroxylase autoantibodies (21OHAb), thyroid function test, Anti TPO, calcium, parathyroid hormone (PTH), LH and FSH, CT of chest and abdomen, and sputum AFB based on the clinical pattern of involvement were performed. Exclusion Criteria: Patients with onset of PAI at infancy and childhood, secondary adrenal insufficiency or exogenous Cushing's syndrome, and central hypocortisolism, including Sheehan's syndrome, were excluded. Results: Thirty-six patients were diagnosed with PAI in this study; 19 (53%) were females and 17 were males (47%). The median age of diagnosis was 35 years. Patients were divided into acute presentation and subacute presentation. Twenty-six patients presented with acute presentation and ten were presented with progressive evolved symptoms. Non-tuberculous etiology was the predominant finding noted in our cohort study (87%, 31 out of 36 patients). The other causes of Addison disease included isolated auto-immune PAI, polyglandular autoimmune syndrome type 1 and II, APLA Syndrome, and adrenal metastasis. Conclusion: Non-tuberculous causes of PAI are the leading etiology in our retrospective study. Autoimmune PAI and Polyglandular autoimmune syndromes are increasingly being recognized as the cause of Addison's disease. PAI individuals require lifelong surveillance for possible development of coexisting autoimmune syndromes and need for glucocorticoid/mineralocorticoid therapy.

Erdheim Chester Disease - Unusual Presentation with Isolated Skeletal Lytic Lesions.

Introduction: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis (LCH) of unknown origin that was first described in 1930. Since then, almost 600 cases have been reported worldwide. Even though this disease primarily affects the bone, it has a varied clinical spectrum of presentation ranging from asymptomatic bone lesions to multisystem involvement. Owing to its protean manifestations ECD is often misdiagnosed or diagnosed late. Case Report: We present a 48-year-old female with a long long-standing history of recurrent bone lesion of the tibia and multiple trivial trauma fractures of long bones. Recently, she also developed a persistent headache and painful swelling of the right shoulder and left hip joint. Radiographs revealed multiple lytic and lytic sclerotic lesions. With the probable diagnosis of LCH, she underwent biopsy which revealed features characteristic of ECD. Conclusion: This case highlights the fact that histopathological confirmation is the key to distinguish various types of histiocytic neoplasms. Overlapping clinical and radiological features with atypical manifestations can occur in both LCH and ECD and does not rule out either of them.

'H-syndrome': a multisystem genetic disorder with cutaneous clues.

We present a case of a 25-year-old man who came to our Endocrine Clinic for evaluation of short stature. He had a history of sensorineural hearing loss, hypertrichosis and hyperpigmentation with the thickening of the skin below the hip, gynecomastia and autoimmune haemolytic anaemia. Investigations showed that he had hypergonadotropic hypogonadism. His phenotype was consistent with that of a rare autosomal recessive genodermatosis of 'H-syndrome'. The diagnosis was confirmed by genetic analysis using next-generation sequencing which showed a homozygous mutation in the SLC29A3 gene (variant: c.1330G>T (p.Glu444Ter)) which was confirmed by Sanger sequencing. This is a rare syndrome with around 100 cases reported in world literature. Though the skin manifestations are pathognomonic of the H-syndrome, it has myriad presentations like short stature, insulin-dependent diabetes mellitus, hypogonadism, hypothyroidism, dyslipidaemia, cardiac anomalies and sensorineural hearing loss. We report this case to highlight the constellation of features of this rare syndrome and bring awareness among the physicians to be vigilant about this syndrome.

Atypical presentation of autoimmune polyglandular syndrome type 1 in the fifth decade.

A 45-year-old woman presented to us with a short-term history of nausea, vomiting and giddiness. On arrival at our hospital, examination revealed postural hypotension. Fluid resuscitation with intravenous normal saline was commenced. She also had chronic mucocutaneous candidiasis and nail changes suggestive of ectodermal dystrophy. Detailed history taking revealed that she had never attained menarche. Serum biochemistries showed hyponatraemia, hyperkalaemia, and hypocalcaemia (sodium, 127 mEq/L; potassium, 6 mEq/L; and albumin-corrected calcium, 6 mg/dL). Adrenocorticotropic hormone-stimulated cortisol (16.7 mcg/dL) was suboptimal favouring adrenal insufficiency. She was started on hydrocortisone and fludrocortisone supplementation. Additionally, the parathyroid hormone was inappropriately low (3.8 pg/mL) confirming hypoparathyroidism. Oral calcium and active vitamin D supplementation were added. With the above clinical and biochemical picture, namely, clustering of primary amenorrhoea, adrenal insufficiency and hypoparathyroidism, the diagnosis pointed towards autoimmune polyglandular syndrome. Genetic workup revealed a deletion in exon 8 of the autoimmune regulator gene confirming the diagnosis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy/autoimmune polyglandular syndrome type 1 .

Is Paget Disease of Bone more Common in South India? Clinical Characteristics, Therapeutic Outcome and follow-up of 66 Patients from Tamil Nadu.

INTRODUCTION: Paget disease of bone (PDB) is a disorder of altered bone remodeling mainly characterized by increased osteoclastic activity. While the exact Indian prevalence remains unknown, a clustering of published cases suggests South Indian predominance. OBJECTIVE: To study the clinico-biochemical profile and therapeutic response of patients with PDB and briefly review the epidemiology of PDB from an Indian perspective. MATERIALS AND METHODS: Retrospective data was collected from the charts of patients who have been seen in endocrine out-patient clinics in Tamil Nadu over a 12-year period. Published literature on PDB from India was reviewed. RESULTS: A total of 66 patients (71% males) predominantly from Tamil Nadu were studied. The mean age at presentation was 67 ± 8 years. Polyostotic involvement was seen in 89% and familial occurrence of PDB in 5 patients. Symptoms at presentation mainly included bone pain (51%) and skeletal deformities (18%). Scalp vein sign (21%) and sensorineural hearing loss (64%) were also noted. Incidental PDB detection by raised serum alkaline phosphatase (SAP) levels was observed in 17% and by abnormal fluorodeoxyglucose-positron emission tomography (FDG-PET) scan in 6% of cases. Mean SAP at presentation was 606 ± 438 IU/L (Normal, 76-140). Major skeletal site involvement includes pelvis (62.1%) and spine (34.8%). Mean (range) follow-up of the cohort was 3.4 yrs (1-12 yrs). In all, 64 subjects received zoledronate and two received alendronate, and mean (SD) SAP at 1-year was 73 ± 42 IU/L. All but two showed remission at the end of 1 year. Two had pathological fractures and two had sarcomas. A review of epidemiology of PDB in Indian literature clearly showed a South Indian predilection for unclear reasons. CONCLUSION: In our cohort of PDB, male gender, polyostotic involvement, and hearing impairment were noted in more than two-thirds of patients and single-dose intravenous zoledronate was effective in normalizing SAP in almost all patients. PDB is intriguingly more common in South India and this needs more exploration.

Hypothalamic-Pituitary-Adrenal Axis Recovery Following the 1-mg Overnight Dexamethasone Suppression Test in Healthy Volunteers.

BACKGROUND: The recovery of hypothalamic-pituitary-adrenal (HPA) axis suppression following pharmacological doses of various steroids has been studied previously. However, no study has been conducted using the more commonly used 1-mg dexamethasone in the overnight dexamethasone suppression test (ODST). Hence, we aimed at evaluating HPA axis recovery after the 1-mg ODST. OBJECTIVES: This study aimed at investigating the pattern and time of recovery of the HPA axis following the 1-mg ODST in healthy subjects. METHODS: Ten healthy volunteers aged 18 - 40 years, BMI < 30 kg/m2, with neither exposure to steroids nor interfering drugs were included. The 1-mg ODST was performed, and the adrenocorticotropic hormone (ACTH) and cortisol samples were withdrawn at regular intervals. The serum cortisol of < 1.8 µg/dL was considered as HPA axis suppression, whereas the cortisol value equal to or more than baseline was deemed as recovery. RESULTS: Cortisol and ACTH levels were suppressed in all subjects 9 hours following the 1-mg ODST. Although ACTH showed an early increase after 8 hours, the upsurge was noticed following 24 hours (mean ± SD, 34.42 ± 18 pg/mL). Later, cortisol accompanied ACTH, and both reached their baseline after 72 hours (mean ± SD, ACTH, 37.48 ± 12.44 pg/mL; cortisol, 8.45 ± 3.32 µg/dL). A small dip in ACTH and cortisol (mean ACTH, 23.84 pg/mL; mean cortisol, 2.3 µg/dL) was observed after 24 - 36 hours indicating the return of the diurnal rhythm before complete recovery. CONCLUSIONS: The complete recovery of the HPA axis occurs only 72 hours following the 1-mg ODST. ACTH begins to recover as early as 8 hours after the maximal suppression and diurnal rhythm of ACTH and cortisol resume 24 to 36 hours later.

Clinical, biochemical and genetic characteristics of children with congenital adrenal hyperplasia due to 17α-hydroxylase deficiency.

Objectives Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder, that could rarely be due to 17 α-hydroxylase deficiency (17αOHD) and/or 17,20 lyase deficiency. Mutation of CYP17A1 gene causes deficiency of glucocorticoids and androgens but excess of mineralocorticoids. Lack of genital ambiguity in most children causes a delay in diagnosis even until puberty. Classical presentation with hypertension and hypokalemia is often not encountered. We intended to study the clinical, biochemical and genetic characteristics of children diagnosed with CAH due to 17αOHD. Methods Three children who were diagnosed with CAH due to 17αOHD in our institute and on follow up were included in this retrospective study. Clinical, biochemical and genetic characteristics of these children were retrieved and studied from electronic medical records. Results Two children were genetic females and one was genetic male, but all three were raised as females. All had hypertension at diagnosis except one but none had hypokalemia. All of them had mutation in the CYP17A1 gene. The two females responded well to oestrogen and progesterone and had adequate estrogenization clinically. Conclusions Even though CAH due to 17αOHD is quite rare, it should be considered while evaluating young individuals with hypogonadism, hypertension with or without hypokalemia. Lack of genital ambiguity and absence of classical signs at presentation does not rule out this not so uncommon condition and warrants follow up.

The Impact of GE Lunar vs ICMR Database in Diagnosis of Osteoporosis among South Indian Subjects.

OBJECTIVE: To study the effect of choosing ICMR reference values on the classification of bone mineral density in Indian patients. DESIGN: Retrospective analysis of Dual Energy X-ray absorptiometry (DEXA) and clinical data. PATIENTS: Totally, 316 patients aged more than 65 years attending a tertiary care hospital in South India who underwent DEXA scan were included in the study. MEASUREMENTS: DEXA scan at femoral neck and lumbar spine. RESULTS: A total of 316 patients were studied. The mean age was 61.98 ± 7.66 years. There were 46.84% females and 53.16% males. The average BMI was 26.37 ± 4.51. Of these patients, 46 had history of hip fracture (14.55%). The adoption of the ICMR normative data resulted in a significant increase in T scores in both the hip (+0.51, P < 0.05) and the spine (+1.64, P < 0.01). The adoption of ICMR normative values, resulted in reduction of osteoporosis prevalence from 26.58% to 5.06%. CONCLUSIONS: There is a clinically significant reduction in diagnosis of osteoporosis with the adoption of ICMR reference standard. Clinicians should be recommended to use raw BMD values in gm/cm2 in FRAX calculation and avoid the use of T scores, to avoid overestimation of fracture risk. If our results are replicated, the implications are enormous - Osteoporosis is currently being over diagnosed.

Sertoli-Leydig cell tumour in a patient with non-classic congenital adrenal hyperplasia: an uncommon duo.

Polycystic ovary syndrome is the most common cause of hyperandrogenism in young females. Other causes are congenital adrenal hyperplasia (CAH), androgen-producing tumours and drugs. The severity and tempo of virilisation help in distinguishing the tumoural from non-tumoural causes. We report a rare case of non-classic CAH and androgen-producing ovarian tumour in the same patient, causing hyperandrogenism. A 15-year-old female patient presented with secondary amenorrhea, excessive facial hair growth and clitoromegaly for 6 months. Due to severe virilisation, tumoural aetiology was considered. Investigations showed marked elevation of testosterone and mild elevation of 17 hydroxy progesterone (17OHP). Imaging confirmed right ovarian tumour. Adrenocorticotropic hormone stimulated 17OHP, was elevated confirming the diagnosis of underlying non-classic CAH. Surgical removal of the tumour was followed by improvement in hyperandrogenism, but persistent elevation of 17OHP confirmed the underlying presence of non-classic CAH.

Effectiveness of Adjuvant Yoga Therapy in Diabetic Lung: A Randomized Control Trial.

CONTEXT: Recent studies provide ample evidence of the benefits of yoga in various chronic disorders. Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia and Sandler coined the term "Diabetic Lung" for the abnormal pulmonary function detected in diabetic patients due underlying pulmonary dysfunction. Yoga therapy may help in achieving better pulmonary function along with enhanced glycaemic control and overall health benefits. AIM: To study the effect of adjuvant yoga therapy in diabetic lung through spirometry. SETTINGS AND DESIGN: Randomized control trial was made as interdisciplinary collaborative work between departments of Yoga Therapy, Pulmonary Medicine and Endocrinology, of MGMC & RI, Sri Balaji Vidyapeeth Puducherry. MATERIALS AND METHODS: 72 patients of diabetic lung as confirmed by spirometry (<70% of expected) were randomized into control group (n=36) who received only standard medical treatment and yoga group (n=36) who received yoga training thrice weekly for 4 months along with standard medical management. Yoga therapy protocol included yogic counseling, preparatory practices, Asanas or static postures, Pranayama or breathing techniques and relaxation techniques. Hathenas of the Gitananda Yoga tradition were the main practices used. Spirometry was done at the end of the study period. Data was analyzed by Student's paired and unpaired 't' test as it passed normality. RESULTS: There was a statistically significant (P < 0.05) reduction in weight, and BMI along with a significant (P < 0.01) improvement in pulmonary function (FEV1, FVC) in yoga group as compared to control group where parameters worsened over study period. CONCLUSION: It is concluded from the present RCT that yoga has a definite role as an adjuvant therapy as it enhances standard medical care and hence is even more significant in routine clinical management of diabetes, improving physical condition and pulmonary function.