Parathyroid Carcinoma Presenting as Recurrent Primary Hyperparathyroidism and Neck Mass: A Case Report.

Parathyroid carcinoma is a rare endocrine neoplasm that accounts for <1% of cases of primary hyperparathyroidism. The management of parathyroid carcinoma is a challenge due to the high rate of local recurrence of the tumour. We report the case of a middle-aged north Indian woman who presented with recurrent primary hyperparathyroidism due to parathyroid carcinoma. She presented with a recurrent palpable hard neck mass and underwent radical dissection of the neck six times. At the time of writing this report, she was referred for external beam radiotherapy to the neck. Parathyroid carcinoma is a rare malignancy with an indolent but tenacious course. Complete resection at the time of initial surgery determines the prognosis of the neoplasm. Chemotherapy and radiotherapy are usually ineffective. Hypercalcaemia needs to be aggressively managed. A multidisciplinary team is required to effectively manage parathyroid carcinoma.

Novel homozygous leptin receptor mutation in an infant with monogenic obesity.

Monogenic obesity can be caused by a mutation in one of the single genes involved in hunger and satiety. The most common mutations affect melanocortin 4 (MC4) followed by the leptin gene and its receptor. Leptin receptor (LEPR) gene mutation is an extremely rare endocrine disease characterized by early-onset obesity, hyperphagia in addition to pituitary hormone deficiency, and metabolic abnormalities. We report the case of a 12-month-old male infant born of a non-consanguineous marriage. He presented to us with rapid weight gain from 2 months of age along with hyperphagia. Biochemistry revealed a deranged lipid profile, elevated transaminases, and markedly raised serum leptin levels. On genetic analysis, a novel mutation was detected, which was a homozygous variation In exon 12 of the LEPR gene (chr1:g.65608901G>A) that resulted in the synonymous amino acid change of lysine at codon 584 proximal to donor splice site (p.Lys584). The in silico prediction of the variant was 'damaging' by MutationTaster2. The mutation was classified as a 'variant of uncertain significance' due to a lack of published literature and had to be correlated carefully with the clinical symptoms. It was recommended to do Sanger sequencing of the parents and other family members. However, due to financial constraints, the family could not afford the same. At the time of writing, funds were being arranged for procuring setmelanotide, which is a novel and effective therapy for monogenic obesity due to LepR mutation.

The spectrum of manifestations of primary hyperparathyroidism in children and adolescents.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a rare disease in children and adolescents. Early recognition of this disease is important to prevent significant morbidity and mortality. MATERIAL AND METHODS: We included 10 consecutive patients with PHPT aged 14 to 19 years of age and followed-up prospectively upto one year after parathyroidectomy. RESULTS: Our cohort included 6 females and 4 males. The mean age of the patients was 16.7 ±1.8 years. The symptoms at presentation were musculoskeletal pain (90%), bone deformity (50%), fracture (30%), proximal myopathy (40%), renal stones (50%), reflux symptoms (40%), and pancreatitis (30%). The mean serum calcium was 3.1 ±0.5 mmol/l, mean serum inorganic phosphorus was 0.9 ±0.3 mmol/l and median serum alkaline phosphatase (ALP) was 1911.5 IU/l (IQR: 522.7-5702.3). The median serum intact parathyroid hormone was 133.5 pmol/l (IQR: 69.5 -178.7) while serum 25(OH)D was 47.7 nmol/l (IQR: 23.7-72.7). Hypercalciuria was observed in 7 patients. Hungry bone syndrome was observed in 4 (40%) patients after surgery. Typical parathyroid adenoma was found in 9 (90%) patients while one patient had atypical adenoma with high mitotic index. After one year of surgery, all patients had significant improvement in clinical and biochemical parameters with persistence of residual bone deformities. CONCLUSIONS: Our study showed the spectrum of manifestations of PHPT in children and adolescents and outcomes of parathyroidectomy till one year. Long-term follow-up studies with bigger cohorts are required to understand the true nature of the disease in children and adolescents.

Adrenocortical adenoma manifesting as Cushing's syndrome and pseudo-precocious puberty in a toddler.

Cushing's syndrome is a rare disease in the paediatric age group. Adrenocortical carcinomas (ACC) constitute the most common cause of Cushing's syndrome between 1 and 5 years of age. Often, adrenocortical carcinomas co-secrete other hormones such as androgens (testosterone), deoxy-corticosterone (DOCA), or 17-hydroxy-progesterone [17(OH)P] in addition to cortisol. This may manifest with symptoms and signs of precocious puberty along with Cushing's syndrome. It is rare for a benign adrenocortical adenoma to co-secrete androgens and other hormones in addition to cortisol. Differentiation between adenoma and carcinoma is difficult in all aspects: clinical, radiological, and histopathological. Here, we describe the case of a 2.5-year-old male child who presented with Cushing's syndrome and virilization. Although we suspected ACC clinically, the radiological and histopathological findings were suggestive of benign adrenocortical adenoma. Our case represents the diagnostic challenge that exists in paediatric adrenocortical tumours.

Atypical parathyroid adenoma: Severe manifestations in an adolescent girl.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a disease that is usually diagnosed in an asymptomatic state during routine biochemical screening. It generally manifests as a sporadic disease in post-menopausal women. However, in India and developing countries, we continue to see severe skeletal and renal manifestations of the disease. CASE REPORT: Herein, we describe the case of a 16-year-old adolescent girl who presented with severe manifestations of primary hyperparathyroidism. Biochemically, she had severe parathyroid hormone (PTH)-dependent hypercalcaemia with hypophosphataemia and vitamin D deficiency (serum total Ca - 18.5 mg/dl [8.5-10.5 mg/dl], serum PO4 - 1.9 mg/dl [2.5-4.5 mg/dl], serum ALP - 2015 IU/l [80-240 IU/l], serum 25[OH]D - 19.1 ng/ml [30-100 ng/ml] and serum iPTH > 5000 pg/ml [15-65 pg/ml]). Pre-operatively, she required management with saline diuresis, bisphosphonate, and calcitonin. After surgery, the patient had severe hungry bone syndrome (serum Ca - 4.1 mg/dl, serum PO4 - 2.1 mg/dl, serum ALP > 10,000 IU/l) that required treatment with calcium infusions for almost 3 months. Although the clinical and biochemical picture was suggestive of parathyroid carcinoma, histopathology revealed atypical parathyroid adenoma with low proliferative index. Atypical parathyroid adenoma is a term applied to a neoplasm with 'worrisome' features but not fulfilling the 'absolute histopathological criteria of malignancy'. CONCLUSIONS: Atypical parathyroid adenoma, a rare cause of PHPT, may be associated with severe manifestations. Although malignancy was not discerned in the immediate post-operative period, we plan to continue long-term follow-up of the patient to look for any signs of recurrence or development of parathyroid carcinoma.

Langherhans cell histiocytosis presenting as primary infertility in a young male.

Langerhans cell histiocytosis (LCH) is a rare clonal neoplastic disorder of Langerhans cells, with an incidence rate of 5 per million individuals. In adults LCH usually affects bone followed by lung, skin, pituitary gland, liver, spleen, and orbits. LCH presenting with endocrinopathy is rare and commonly involves posterior pituitary with central diabetes insipidus (DI). Here, we present a rare case of LCH involving posterior pituitary but presenting as infertility in a 25-year-old married man. Later the thyroid gland was also found to be involved in the form of multiple nodules. Fine needle aspiration cytology (FNAC) from right lobe of thyroid showed sheets of Langerhans cells along with entrapped residual thyroid follicular cells which were further confirmed by immunocytochemistry as well as cell block preparation followed by immunohistochemistry. A final diagnosis of LCH involving pituitary and thyroid was made and patient was then started on treatment according to LCH treatment protocol LCH III-6 consisting of prednisolone and vinblastine (6 weeks with daily 40 mg/m2 oral prednisolone, and 6 mg/m2 i.v. vinblastine every 7 days). Patient is responding well to the therapy and is on follow up.

Endocrine causes of heart failure: A clinical primer for cardiologists.

Heart failure (HF) may be a presenting manifestation of a few endocrine disorders and should be considered in evaluation of heart failure causes. This clinically oriented review is an attempt to highlight the protean manifestations of heart failure in endocrine diseases which could present either as acute or chronic heart failure. Acute heart failure manifests as hypertensive crisis, Takotsubo syndrome, or as tachy/brady cardiomyopathies. Chronic heart failure could masquerade with features of hyperdynamic heart failure, or hypertrophic, restrictive or dilated cardiomyopathy. Rarely constrictive features or resistant heart failure could be the presenting feature. Isolated presentation as pulmonary hypertension and right heart failure are also documented. Good history-taking and physical examination with targeted investigations will help in the timely management for reversing the pathophysiology to a significant extent by appropriated management.

Primary Sjögren's syndrome manifesting as sclerotic metabolic bone disease.

Primary Sjögren's syndrome (pSS) is a chronic slowly progressive autoimmune disease characterised by lymphocytic infiltration of salivary and lacrimal glands with varying degree of systemic involvement. Renal involvement, a recognised extraglandular manifestation of pSS, is commonly related to tubular dysfunction and generally manifests as distal renal tubular acidosis (RTA), proximal RTA, tubular proteinuria and nephrogenic diabetes insipidus. Untreated long-standing RTA is known to cause metabolic bone disease. Here, we present the report of a patient with sclerotic metabolic bone disease related to pSS with combined distal and proximal RTA and negative workup for other causes of sclerotic bone disease. A significant clinical and biochemical improvement, including recovery of proximal tubular dysfunction, was noted with alkali therapy. This case suggests the need to consider pSS in the diagnostic algorithm of a patient presenting with sclerotic bone disease.

Renal Tubular Acidosis Manifesting as Severe Metabolic Bone Disease.

Renal tubular acidosis (RTA) is a condition characterized by normal anion gap metabolic acidosis. Type 1 and type 2 RTA are the most common, and are caused by defective secretion of hydrogen ions and impaired absorption of bicarbonate, respectively. Long-standing uncorrected acidosis can lead to metabolic bone disease (MBD). Rickets and osteomalacia remain the commonest manifestations of uncorrected RTA. In addition, there can be a myriad of other skeletal manifestations like fractures, pseudofractures, secondary osteoporosis and even sclerotic bone disease. The postulated mechanism for bone involvement includes acidosis-mediated exaggerated osteoclastic bone resorption. Other contributory factors include abnormal renal handling of phosphate leading to hypophosphataemia in proximal RTA, and impaired vitamin D metabolism and action. In distal RTA, hypercalciuria and secondary hyperparathyroidism may play a key role for bone involvement. Recognizing the disease in its early course is important to prevent permanent sequelae of skeletal involvement. Most of these patients may, in fact, undergo orthopaedic interventions without primary correction of acidosis. We describe five cases who presented with MBD in varied forms. While evaluating the aetiology of MBD, they were diagnosed with RTA. Subsequently, we attempted to analyse the causes of RTA. Although the common causes were ruled out, genetic aetiology could not be ascertained due to resource constraints. RTA remains an important differential diagnosis of MBD. More awareness is required to diagnose the disease early and to treat it adequately. Our case series is an attempt to provide the clinical, biochemical and skeletal spectrum of RTA. In addition, we have attempted to provide algorithms for the approach and evaluation of RTA along with their varied causes.

X-Linked Hypophosphatemic Rickets Manifesting as Sclerotic Bone Disease and Enthesopathy.

X-linked hypophosphatemic (XLH) rickets is a genetic disease caused due to the inactivation of the PHEX gene (phosphate regulating gene with homology to endopeptidase on the X chromosome). The usual presentation is with rickets and osteomalacia, and dental abscesses leading to premature loss of teeth. However, enthesopathy and sclerotic bone disease in XLH have also been reported in a few case reports. In this report, we describe the case of a 23-year-old female patient who presented to us with severe bone deformities, proximal myopathy, truncal weakness, and recent onset of pain and stiffness around the joints. She was diagnosed with XLH and was found to have severe enthesopathy along with heterotopic ossification.

46, XY complete gonadal dysgenesis with pubertal virilisation due to dysgerminoma/gonadoblastoma.

Complete gonadal dysgenesis (CGD) or Swyer syndrome is characterised by sexual infantilism in a phenotypic female with 46, XY karyotype. Patients with gonadal dysgenesis and Y-chromosome material are at a high risk of developing gonadoblastoma and dysgerminoma. A 16-year-old girl presented with progressive virilisation, poor breast development and primary amenorrhea. On evaluation, she was found to have male-range serum testosterone, large abdominopelvic mass lesion, elevated germ cell tumour markers and 46, XY karyotype. She underwent surgical excision of left gonadal mass and right streak gonad, histopathology of which revealed dysgerminoma and gonadoblastoma, respectively. A diagnosis of virilising germ cell tumour arising in the setting of 46, XY CGD was, therefore, made. This case highlights a rare presentation of 46, XY CGD and the need to consider early prophylactic gonadectomy in patients affected with this rare condition. The presence of dysgerminoma/gonadoblastoma should be suspected if a hitherto phenotypic female with CGD undergoes virilisation.

Spontaneous Conception, Pericardial Effusion, and Pseudohypertrophic Myopathy Mimicking Muscular Dystrophy in Delayed Presentation of Sheehan Syndrome.

Sheehan syndrome, characterized by postpartum pituitary necrosis, is an important cause of hypopituitarism in developing countries. We report the case of a 50-year-old female with Sheehan syndrome, who had two spontaneous conceptions following severe postpartum hemorrhage in her first delivery and presented 27 years later with moderate pericardial effusion and features of pseudohypertrophic myopathy mimicking muscular dystrophy.

Multiple Endocrine Neoplasia Type 1 Syndrome: A Case Report and Review of Literature.

Multiple endocrine neoplasia type 1 (MEN1) or Wermer's syndrome is a genetic disease characterized by involvement of multiple endocrine glands, primarily involving parathyroid, pancreas, and pituitary. Other additional features include foregut carcinoids; non-functioning adrenal tumors; and skin lesions such as lipomas, collagenomas, and angiofibromas. Here, we describe our experience in managing a patient who presented to us with spontaneous episodes of hypoglycemia and was diagnosed with insulinoma. Detailed clinical and biochemical evaluation unraveled the diagnosis of MEN1 in the patient and her family members who constituted a large kindred. This case highlights the importance for evaluation of MEN1 in a patient or his/her family members in the setting of clinical and biochemical suspicion. In addition, we have also discussed the utility of the latest diagnostic and therapeutic modalities for management of MEN1.

Male Gender Identity and Reversible Hypokalemic Hypertension in a 46,XX Child with 11-Beta-Hydroxylase Deficiency Congenital Adrenal Hyperplasia.

Steroid 11-beta-hydroxylase deficiency is a relatively rare form of congenital adrenal hyperplasia (CAH). We describe the case of a 46,XX child, reared as a male, who first presented to us at the age of three years with features of peripheral precocity and hypokalemic hypertension. Based on the clinical and biochemical profile, a diagnosis of 11-beta-hydroxylase deficiency CAH was established, and physiological glucocorticoid replacement was begun. Both hypertension and hypokalemia improved with glucocorticoid supplementation, and at eight years of age, antihypertensives were successfully withdrawn. Regression of left ventricular hypertrophy was also noted at this time. In keeping with the male gender identity, the child underwent hysterectomy, oopherectomy and breast reduction surgery at 13 years of age. We conclude that both hypertension and end-organ damage due to 11-beta-hydroxylase CAH may get reversed following optimal glucocorticoid treatment. Detailed genital examination at birth may help in early diagnosis of this rare disorder, thereby preventing the deleterious consequences of longstanding mineralocorticoid excess.

Brown Tumor as an Index Presentation of Severe Vitamin D Deficiency in a Teenage Girl.

Brown tumor is a non-neoplastic fibro-cystic expansile bone lesion caused by parathyroid hormone excess. It has been commonly described in patients with primary hyperparathyroidism and secondary hyperparathyroidism due to chronic kidney disease. However, it is very rare to encounter a brown tumor in the setting of nutritional vitamin D deficiency. We describe the case of a 16-year-old girl who presented with brown tumor-like lytic lesion of femur caused by severe longstanding vitamin D deficiency. Treatment with elemental calcium and cholecalciferol resulted in correction of hyperparathyroid state, with the resultant disappearance of the bony lesion and remarkable symptomatic improvement. Unnecessary orthopaedic intervention may be avoided using a high index of suspicion and performing targeted investigations in such cases.