Primary Hyperparathyroidism in Young and Adolescents: Alike or Unlike Adult Hyperparathyroidism? - A Series from South India.

Background: Primary hyperparathyroidism (PHPT) is a common endocrine condition but rare in the pediatric and adolescent populations. The presentations can be unique, accounting for significant morbidity in the case of untimely detection. Aim: To study surgically treated pediatric PHPT retrospectively. Methods: Surgically treated children of PHPT up to 20 years of age between 2010 to 2022 were analyzed. All of them were operated on by an endocrine surgeon and team. Results: There was a total of 712 parathyroidectomies over 12 years, out of which there were 52 children (7.3%) had PHPT at less than 20 years of age. This group included 32 male children. The mean age was 16.1 years, including 7 cases of neonatal severe HPT. Multiple Endocrine Neoplasia type 1 was confirmed in 12 children. Presentations were more severe like bone pain (35.13%), renal stones (27.02%), incidental asymptomatic detection (18.9%), failure to thrive (10.8%), and pancreatitis (8.1%) as compared to adults. Mean serum calcium was 12.9 mg/dl (highest-14.1, N-8.8-10.8 mg/dl), mean parathormone levels were 386.91 pg/ml (N-10-65) and vitamin D levels ranged from 2.9-22.8 ng/ml. Localization was done with ultrasound and 99mTc- SESTAMIBI scans. Mean serum calcium levels in NSPHPT were 28.6 mg/dl (N-8.8-10.8 mg/dl). There were a total of 45 cases (6.32%) of PHPT less than 20 years of age, excluding the cases of NSPHPT. All children underwent parathyroidectomy, with 14 cases having an additional thymectomy, 2 cases with thyroidectomy, and a single case of hemithyroidectomy. The cure rate was 97.3%, while one baby with NSPHPT had persistent disease (postop PTH-110 pg/ml). The uniglandular disease was seen in 54.05% and the rest had a multiglandular disease. Adults accounted for 559/660 cases with 80% uniglandular disease. All cases had a postoperative histopathological confirmation with an average follow-up of 1 year. Conclusion: Childhood PHPT has a few features same as the adult population. Symptomatic presentations like adults, though pancreatitis and fatigue were more commonly seen as compared to bone pain. Calcium, phosphorus, and parathormone levels were comparable. Uniglandular involvement was seen just like the adult population. There are a few others that make them a distinct subtype like their symptoms of bone pain and being more common among boys. One-fourth of them had MEN1. Fewer cases in this age group make them unique.

Our Uncommon Experience with 6 Cases of Riedel's Thyroiditis (Woody Thyroiditis).

Riedel's thyroiditis is a rare form of thyroiditis. Estimated prevalence is 1.06/100,000 population and is reported in 0.05% of thyroidectomy specimens. It has 38% association with systemic fibrotic conditions. We retrospectively reviewed 6 cases of Riedel's thyroiditis at a tertiary care centre in south India, from 2011 through 2019 with special emphasis on demography, clinical presentation, workup, management, intraoperative findings, postoperative outcomes and follow up. There were 4 females and 2 males of which we reported a rare presentation in paediatric age group which was probably never reported before. Presenting symptoms included dysphagia and compressive symptoms in neck. 5 out of 6 cases underwent surgical management- 4 total thyroidectomy and 1 hemithyroidectomy. Postoperative complications noted were temporary hypoparathyroidism, unilateral vocal cord palsy and temporary bilateral vocal cord palsy One case was medically managed with oral corticosteroids. There was no evidence of extra cervical fibrosis on follow up in all patients. There was no cause-specific mortality, and the fibrotic process stabilized or resolved in all patients. Riedel's thyroiditis is a fibroinflammatory disorder presenting with compressive symptoms mandating surgical intervention mainly decompression in the form of isthmectomy. However since extensive interventions are associated with complications it is less favoured approach. Long term follow up of these cases are necessary for detecting evidence of extra cervical fibrosis.

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.

Neonatal Severe Primary Hyperparathyroidism: A Series of Four Cases and their Long-term Management in India.

CONTEXT: Neonatal severe primary hyperparathyroidism (NSPHPT) is an extremely rare autosomal recessive disorder, requiring a high index of suspicion. Infants affected with this disorder present with severe life-threatening hypercalcemia early in life, requiring adequate preoperative medical management followed by surgery. AIMS: We report four newborns with NSPHPT who were managed over 10 years. SUBJECTS AND METHODS: Demography, clinical presentation, treatment, and follow-up data were retrospectively studied with descriptive analysis to highlight the utility of long-term medical management, surgery, and genetic testing reported in the literature. STATISTICAL ANALYSIS USED: Descriptive Analysis. RESULTS: We had three males and one female infant with a mean age of diagnosis at 28.7 days, calcium 29.2+/-2.8 mg/dL, and parathormone (PTH) 1963+/-270.4 pg/mL. All four infants presented with failure to thrive, hypotonia, and respiratory distress. All infants were treated medically followed by total parathyroidectomy plus transcervical thymectomy, with an additional hemithyroidectomy in one of them. Imaging was negative in all four cases. Three babies became hypocalcemic while the fourth infant had a drop in PTH and is on the tab. cinacalcet 30 mg/day. CaSR mutation was positive in three infants. CONCLUSIONS: Diagnosing NSPHPT needs expert clinical acumen. It requires emergency medical management to control calcium levels. The crisis may present later, necessitating parathyroidectomy in these cases once the child is fit for surgery. Surgery offers a cure for this unusual lethal hypercalcemia while the role of cinacalcet needs a special mention. Sound knowledge in endocrinology with parathyroid embryology and morphology is of paramount importance. Our case series might add a few insights into managing this unusual genetic disorder.

Prevalence and implications of thyroid related embryological remnants: A prospective study of 1118 total thyroidectomies.

CONTEXT: Modern thyroid surgery has undergone a paradigm shift from subtotal thyroidectomy to an extended total thyroidectomy (TT) even for benign disorders. This entails removal of all embryological remnants even in benign disorders. AIMS: To study the prevalence of various embryological remnants of the thyroid and surgical utility and implications in preventing complications. SETTINGS AND DESIGN: Retrospective study of total thyroidectomies done by a single endocrine surgeon by standardized technique. METHODS AND MATERIAL: A detailed search of all embryological rests including Pyramidal tract (PT), Tubercle of Zuckerkandl (TZ), and Thyro-thymic thyroid rests (TTR) were done in 1118 patients undergoing TT over 6 years. The cases with and without TTR were divided as Group A and B, respectively. Their prevalence and impact on parathyroid preservation and other clinical parameters were analysed. STATISTICAL ANALYSIS USED: Descriptive analyses. RESULTS: Out of the 1118 TT cases, TTR was seen in 230 (20.57%) cases, TZ in 598 (53.48%), cases and PT in 641 (57.33%) cases. Among group-A (n = 230), 213 had unilateral and 17 had bilateral TTR with 51 (22.17%) having retrosternal extension. Compressive symptoms, presence of TZ and PT were also significantly higher in group A. On follow up the incidence of temporary hypoparathyroidism was significantly higher in group-A, where as permanent hypoparathyroidism, temporary and permanent vocal cord palsy were comparable between the two study groups. CONCLUSIONS: Embryological remnants related to thyroid are not uncommonly encountered during total thyroidectomy. A thorough search and complete removal is crucial for the successful outcome of the procedure.

Is 3-4 Weeks Required for TSH to Rise Post Thyroidectomy? A prospective Study and Discussion of its Implications on Patient Care.

CONTEXT: In patients with differentiated thyroid cancer (DTC), for the purpose of radioiodine (131I) whole-body scan and treatment of remnant, or residual tumor, or metastatic disease, thyroid hormone withdrawal remains the standard approach for raising thyroid-stimulating hormone (TSH) levels to ensure adequate radioiodine uptake. Thyroid hormone is withdrawn 3-4 weeks prior radioiodine therapy (RAIT) to allow the serum-TSH concentration to rise to above 25-30 mU/L. AIMS: We studied the time taken for TSH to rise in 40 patients after total thyroidectomy operated for DTC. SETTINGS AND DESIGN: Prospective observational study. METHODS AND MATERIALS: 40 patients with proven differentiated thyroid cancer attending a tertiary care center were studied. STATISTICAL ANALYSIS USED: Data was analyzed by using SPPSS software for windows (version 15, SPSS Inc., Chicago, USA). RESULTS: After performing preoperative TSH in all patients excluding preoperative TSH elevation, it was planned to collect weekly postoperative samples till TSH ≥30. The mean (standard deviation, SD) age of the cohort was 40 (13) years with 35 females (88%) and their mean (SD) preoperative TSH was 3.6 (1.35) mIU/L. At the end of the first week postoperatively, the mean TSH of the cohort was 24.25 (6) with 8 patients (20%) achieving the cut-off of TSH ≥30 mIU/L and 30 patients (75%) achieving TSH level ≥20 mIU/L. At the end of the second week, the mean TSH was 53 (17) with all patients (100%) achieving a TSH level >30 mIU/ml. CONCLUSIONS: An iodine whole-body scan can be performed in 10-14 days after total thyroidectomy instead of the usual wait time of 4 weeks. This could improve patient QOL and avoid complications related to prolonged hypothyroidism.

The Impact of Thyroiditis on Morbidity and Safety in Patients Undergoing Total Thyroidectomy.

BACKGROUND: The indications for surgery in thyroiditis vary from compressive symptoms to cosmesis. We analyzed the complications in patients who underwent total thyroidectomy (TT) in goiters associated with thyroiditis. MATERIALS AND METHODS: This retrospective study was done in an endocrine surgical center over 4 years. A total of 724 patients, who underwent TT for benign thyroid disorders, were included in the study. Patients were divided into two groups based on histopathology into Group A (nonthyroiditis cases) and Group B (thyroiditis cases); Group B is subdivided into Group B1 (nodular goiter with associated thyroiditis) and Group B2 (Hashimoto's thyroiditis). The preoperative parameters analyzed were serum calcium, serum Vitamin D, serum parathyroid hormone (PTH), and vocal cord status. The intraoperative parameters observed were operating time, parathyroid preservation, and autotransplantation and course of recurrent laryngeal nerve (RLN). Postoperative parameters monitored were serum calcium, serum PTH, serum magnesium, signs and symptoms of hypocalcemia, and vocal cord status. Follow-up was done at 6 months with serum calcium, serum PTH, and video laryngoscopy. RESULTS: Both groups were age and sex matched. All preoperative and intraoperative parameters were comparable among groups. Both transient complications (<6 months) were higher in Group B than A. Transient hypocalcemia was higher in Group B (39.70%) than Group A (24.77%) (P = 0.001). Transient hypocalcemia was higher in Group B1 (36.58%) than Group B2 (44.44%) (P = 0.014). Transient RLN palsy was higher in Group B (9.55%) than Group A (7.52%) (P = 0.040). Transient RLN palsy was higher in Group B1 (8.53%) than Group B2 (11.11%) (P = 0.039). Permanent hypoparathyroidism and permanent RLN palsy were comparable between the Groups A and B and between Groups B1 and B2. CONCLUSION: The incidences of transient complications are higher in patients with thyroiditis. Careful analysis of surgical indications will avoid unnecessary surgery in thyroiditis cases.

A Prospective Study on Role of Supplemental Oral Calcium and Vitamin D in Prevention of Postthyroidectomy Hypocalcemia.

BACKGROUND: Postoperative transient hypocalcemia is sequelae of total thyroidectomy (TT), which is observed in up to 50% of patients. Routine oral calcium and Vitamin D supplementation have been proposed to prevent symptomatic hypocalcemia preventing morbidity and facilitating early discharge. PATIENTS AND METHODS: A total of 208 patients with nontoxic benign thyroid disorders, undergoing TT, were serially randomized into four groups: Group A (no supplements were given), Group B (oral calcium - 2 g/day given), Group C (calcium and calcitriol - 1 mcg/day are given), and Group D (calcium, calcitriol, and cholecalciferol - 60,000 IU/day are given). Patients were monitored for clinical and biochemical hypocalcemia (serum calcium, [Sr. Ca] <8 mg/dl), along with serum intact parathormone (Sr. PTH) and magnesium 6 h after surgery and Sr. Ca every 24 h. Intravenous (IV) calcium infusion was started, if any of the above four groups exhibit frank hypocalcemia. Patients are followed up with Sr. Ca and Sr. PTH at 3 and 6 months. RESULTS: All groups were age and sex matched. Hypocalcemia was observed in 72/208 (34.61%) cases. Incidence of hypocalcemia was higher in Group A (57.69%) and Group B (50%) compared to Group C (15.38%) and Group D (15.38%). Hypocalcemia necessitating IV calcium occurred in 31/208 (14.90%) patients. IV calcium requirement exceeded in Group A (26.92%) and Group B (23.07%) compared to Group C (5.76%) and Group D (3.84%). There was no statistical difference in basal levels of serum Vitamin D, calcium, magnesium, intact PTH, and 6 h after surgery. Permanent hypoparathyroidism developed in five patients on follow-up. CONCLUSION: Routine postoperative supplementation of oral calcium and Vitamin D will help in the prevention of postthyroidectomy transient hypocalcemia significantly. Preoperative Vitamin D levels do not predict postoperative hypocalcemia.

Hypercalcaemic encephalopathy due to metastatic parathyroid carcinoma.

A 49-year-old man presented in the emergency department with altered sensorium and renal failure and was placed on a ventilator. Evaluation with MRI of the brain showed enhancing lesion in the occipital lobe. Biochemical tests revealed elevated calcium and parathyroid hormone (PTH) levels. Further evaluation revealed multiple lesions at both lobes of the lungs and nodular lesion in the right inferior pole of the thyroid. Diagnosis of metastatic parathyroid carcinoma was suspected. Patient was stabilised with bisphosphonates and haemodialysis and planned for surgery. Intraoperatively a hard lesion was found in the right inferior parathyroid infiltrating the surrounding structures. En bloc resection was done. General condition of the patient improved and he was weaned from the ventilator. Histopathology confirmed the diagnosis of parathyroid carcinoma. Postoperatively, there was persistent elevation of PTH in spite of a fall in calcium levels indicating functioning brain and pulmonary metastases. Due to extensive metastases, the patient was given palliative cinacalcet and was kept under follow-up.

Does Time of Sampling or Food Intake Alter Thyroid Function Test?

CONTEXT: A common question from most patients or laboratories is whether blood sample for thyroid-stimulating hormone (TSH) and free T4 (fT4) needs to be collected in a fasting state and whether time of the day when sample is collected matters. AIMS: The aim of the study was to study the impact of the time of day and food intake on levels of TSH and fT4. SETTINGS AND DESIGN: Cross-sectional prospective data collection. SUBJECTS AND METHODS: We prospectively collected data from 52 volunteers who were not known to have any thyroid disorder and were not on any thyroid-related medication. Blood samples for TSH and fT4 were collected on day 1 at 8 am and 10 am with the patient remaining in the fasting state till the collection of the second sample at 10 am. On day 2, samples were collected at 8 am (fasting state) and at 10 am (2 h postprandial state). In 22 volunteers from the group, the tests were performed in three common assay techniques including chemiluminescent assays (chemiluminescent immunoassay [CLIA] and chemiluminescent microparticle immunoassay [CMIA]) and enzyme-linked fluorescence assay. RESULTS: The mean (standard deviation) and median (interquartile range) TSH during the extended fast on day 1 were 2.26 ± 1.23 and 2.19 (1.21-3.18), which was significantly lower than the fasting TSH performed on day 1 (P < 0.001). Similarly, the values of TSH 2 h postmeal on day 2 of the testing (mean 1.93 ± 1.12; median 1.64 [1.06-2.86]) were significantly lower than TSH performed in the fasting state on day 2 (P < 0.001). The mean fT4 value was 1.01 ± 0.15 with median of 0.99 (0.91-1.11) in the fasting state and there was no significant difference between the fT4 values performed during fasting, extended fasting, and postmeal state. Among the volunteers in whom the test was performed in the three different assay techniques, the TSH was not statistically different either in the fasting (P = 0.801), extended fasting (P = 0.955), and postprandial samples (P = 0.989). The fT4 values did not vary significantly when done by the same assay method. However, the fT4 levels varied significantly (P < 0.001) when done by another assay method. CONCLUSIONS: We conclude stating that the timing of the test affects TSH values and this should be factored in making decisions in diagnosis of subclinical hypothyroidism.

Fasting practices in Tamil Nadu and their importance for patients with diabetes.

Religious practices and cultural customs related to eating habits have a significant impact on lifestyle and health of the community. The Ramadan fasting in Muslims and its influence on various metabolic parameters such as diabetes have been reasonably studied. However, literature related to Hindu religious customs related to fasting and food patterns during various festivals and its effect on diabetes are scarce. This article is an attempt to describe the Hindu religious customs related to fasting and food practices from the State of Tamil Nadu (South India) and to raise the awareness among physicians about its relationship with diabetes which may help in managing their diabetic patients in a better way.

EBSLN and Factors Influencing its Identification and its Safety in Patients Undergoing Total Thyroidectomy: A Study of 456 Cases.

BACKGROUND: The external branch of the superior laryngeal nerve (EBSLN) is at surgical risk during superior thyroid pole ligation during thyroidectomy. Majority of studies have addressed the identification of these nerves and its reported incidence. Very few studies have addressed the relationship of these nerves with the volume of the thyroid gland and presence of toxicity. MATERIALS AND METHODS: A retrospective evaluation of 456 patients who underwent total thyroidectomy were analysed from the prospectively maintained database. The EBSLN was diligently identified and preserved before individual ligation of the superior thyroid pedicle. The nerve was graded as per the Cernea classification (type I, IIa and IIb). Goitres are classified into toxic & non-toxic based on hyperthyroidism, further sub classified as large (>50 cc) and small (≤50 cc) based on volume of each lobe. The grading of EBSLN was correlated with hyperthyroidism and volume of each lobe. RESULTS: In 456 patients (912 nerves), EBSLN was identified in 849/912(93.09%), type I in 156/912(17.1%), type IIa in 522/912(57.23%) and type IIb in 171/912(18.75%). The prevalence of large goitres was 180/912(19.73%).Type IIb nerve was predominantly seen in 161/180(89.4%) of large goitres. Type IIb nerves was more common in toxic 141/372(37.9%) than non-toxic lobes 25/540(5.46%). CONCLUSION: Large goitres are not uncommon in toxic cases. The EBSLN is at highest risk of injury in this subgroup of patients and surgical expertise is essential to identify this entity of EBSLN to perform a safe thyroidectomy.

A Prospective Study on Cardiovascular Dysfunction in Patients with Hyperthyroidism and Its Reversal After Surgical Cure.

BACKGROUND: Cardiovascular dysfunction (CVD) is a major cause of mortality and morbidity in hyperthyroidism. CVD and its reversibility after total thyroidectomy (TT) are not adequately addressed. This prospective case-control study evaluates the effect of hyperthyroidism on myocardium and its reversibility after TT. MATERIALS AND METHODS: Surgical candidates of new onset hyperthyroidism, Group A (n = 41, age < 60 years) was evaluated with 2D Echocardiography, serum n-terminal probrain natriuretic peptide (NT-proBNP) at the time of diagnosis (Point A), after achieving euthyroidism (Point B) with antithyroid drugs, and 3 months after TT (Point C). 20 patients with nontoxic benign thyroid nodules undergoing TT served as controls (Group B). RESULTS: Both groups were age and sex matched. Group A (n = 41) comprises Graves disease (n = 22) and Toxic Multinodular goiter (n = 19). At point A, CVD was evident in 26/41(63.4%), pulmonary hypertension (PHT) in 24/41(58.5%)--mild in 17/41(41.4%) and moderate in 7/41(17%)--dilated cardiomyopathy (DCM) in 8/41(19.5%), heart failure in 4/41(9.7%), and NT-proBNP elevated in 28/41(68.3%). At point B, recovery was observed in PHT 19/26(73.1%), DCM 4/8(50%), heart failure 4/4(100%), NT-proBNP in 3/28(10.7%). At Point C, further improvement occurred in PHT 23/24(95.8%), DCM 7/8(87.5%), heart failure 4/4(100%), and NT-proBNP in 24/28(85.7%). CONCLUSION: Pulmonary hypertension is completely reversible at 3 months after TT and is the most common cardiac event in Hyperthyroidism. Various parameters of CVD improved consistently after surgical cure. NT-proBNP levels correlated well with the severity and duration of CVD and hence can be an objective tool in monitoring of hyperthyroid cardiac dysfunction.

Unusual diagnosis of a solitary thyroid nodule in the paediatric population: cervical thymic cyst.

We present a case of an 8-year-old girl with a painless swelling in her neck. An ultrasonogram revealed a cystic nodule with internal echoes, lying posterior to right lobe of thyroid, and MRI confirmed it. Thyroid scintigraphy did not show any uptake in the swelling. Intraoperatively, the lesion was densely adherent to the thyroid gland, hence a hemithyroidectomy was performed. Histopathology showed it to be an ectopic cervical thymic cyst with parathyroid tissue.

Non-elevation of TSH after total thyroidectomy: a surgical surprise.

A 31-year-old woman with papillary carcinoma of the thyroid with right cervical lymph nodal metastasis underwent total thyroidectomy with modified radical neck dissection. At follow-up 6 weeks after surgery, she had not developed clinical features of hypothyroidism and her thyroid-stimulating hormone (TSH) was within normal limits. Further evaluation including technetium scintigraphy of the thyroid and MRI of the chest confirmed thyroid tissue, thyrothymic thyroid rest (TTR), in the superior mediastinum. The patient's TSH elevated well after reoperation of TTR. She underwent radioiodine ablative therapy and suppressive thyroxine therapy as per the protocol for well-differentiated thyroid cancer follow-up. The clinical importance of these embryological rests of thyroid tissue, especially in the management of thyroid malignancies, is discussed in this report.