A Case Reported With 46, XX Testicular Disorders Of Sexual Development And Its Possible Association With Dysembryoplastic Neuroepithelial Tumour.

The main factor determining differentiation of bipotential gonads into testes or ovaries is the presence or absence of SRY (sex-determining region on Y chromosome) gene. De la Chapelle syndrome is a chromosomal anomaly with chromosomal makeup of a female (46, XX) and phenotypic presentation of a male. Previously known as XX sex reversal, it is now called 46, XX testicular disorders of sexual development (DSD). Although rare, it presents as a major chromosomal anomaly, with SRY gene crossover proposed as an underlying aetiology in most patients. We report the case of a 25-year-old male who presented with infertility and was diagnosed with De 46, XX testicular DSD. He has a previous history of resected dysembryoplastic neuroepithelial tumour (DNT). The differential diagnosis of 46, XX DSD and possible association/coincidental finding of DNT have been discussed. Karyotyping should be a part of the workup for every patient who presents with infertility and has azoospermia and hypergonadotropic hypogonadism.

Frequency of hashimoto thyroiditis in papillary thyroid cancer patients and its impact on their Outcome.

BACKGROUND: Hashimoto thyroiditis (HT) is an autoimmune disorder of thyroid gland and is the most common cause of hypothyroidism. Its association with thyroid lymphoma is well established but with papillary thyroid cancer (PTC), the studies have shown inconsistent results. METHODS: It is a retrospective review of papillary thyroid cancer patients and 213 participants were included for final analysis. They were divided in two groups, based on presence or absence of Hashimoto thyroiditis. We noted their demographic details, histopathological diagnosis, presence of thyroid autoantibodies, TNM staging, outcome and duration of follow up. RESULTS: The frequency of Hashimoto thyroiditis in papillary thyroid cancer patients was found to be 34.27% (73). In Hashimoto thyroiditis and PTC patients, more patients were in T1 and T2 stage, i.e., 27.4% and 38.4% as compared to PTC alone group, who had more patients with T3 and T4 disease 44.3% and 5% respectively. Although lymph node metastasis was more common in PTC with Hashimoto thyroiditis 56.2%, but distant metastasis was observed more in isolated PTC group 14.3%. Cure was observed in 75.3% and 47.1% in PTC patients with and without Hashimoto thyroiditis respectively. While 22.9% patients having isolated PTC had persistent disease as compared to 6.8% when PTC was accompanied with Hashimoto thyroiditis. CONCLUSIONS: The papillary thyroid cancer patient who had concomitant Hashimoto thyroiditis, had a less aggressive disease in terms of T stage and distant metastasis and they had a better outcome in terms of higher cure rate and less persistent disease as compared to the papillary thyroid cancer without Hashimoto thyroiditis.

Malignant and Non-Malignant Causes of Hypercalcemia: A Retrospective Study at a Tertiary Care Hospital in Pakistan.

BACKGROUND: Hypercalcemia is a common electrolyte abnormality presenting with a variety of symptoms. The common causes are primary hyperparathyroidism and malignancy associated with hypercalcemia. However, iatrogenic hypercalcemia with the overzealous use of vitamin D has now emerged as another important cause of hypercalcemia over the past decade. OBJECTIVE: This study aims to evaluate the causes of hypercalcemia, management strategies, and outcomes in patients admitted with hypercalcemia in a tertiary care hospital.  Method: It is a retrospective study done at Aga Khan University Hospital (AKUH), Karachi after taking approval from the ethical review committee (ERC). Data were gathered about all patients admitted from 1st January 2008 to 31st December 2018. A total of 1142 patients were included in the study and their calcium levels were noted. Along with demographic details, data pertaining to their diagnosis and all investigations done to evaluate the causes of hypercalcemia were noted in a pre-defined questionnaire. RESULTS: A total of 814 patients having hypercalcemia were included in the final analysis and their mean age was 60.8 ± 14.1 years. Male and female patients were 45.4% and 54.6%, respectively, and their mean hospital stay was 6.2 ± 5.8 days. The most common cause of hypercalcemia was malignant solid tumors (49.1%), followed by hematological malignancy (16.5%), hyperparathyroidism (10.9%), definite vitamin D toxicity (8%), chronic kidney disease (4.9%), chronic granulomatous diseases (4.7%), and probable vitamin D toxicity (3.5%). The oral cavity carcinoma (17.7%) was the most common solid tumor associated with hypercalcemia. Amongst hematological malignancy, multiple myeloma (14.4%) was the most common one. Out of 814 patients admitted with hypercalcemia, 601 (74%) patients recovered from hypercalcemia, while mortality was observed in 129 (16%) patients. Of those who expired, 110 (85.3%) had malignancy either solid tumor or hematological. CONCLUSION: Malignancy is the most common cause of hypercalcemia in admitted patients. The knowledge of hypercalcemia's causes is of great importance so that targeted investigations can be done. Not only will it minimize the cost burden and shorten the hospitalization of patients; it will also help the physicians to decide the appropriate management accordingly. Moreover, vitamin D toxicity was also observed in a significant number of patients which highlights the common practice of using higher doses of vitamin D by physicians.

A Case Report Emphasizing the Importance of Early Diagnosis and Management of Intracranial Germinoma.

Intracranial germ cell tumors (GCTs) account for 3%-5% of all intracranial tumors. They commonly manifest during first two decades of life. We are reporting a case of a young female, who presented with progressive visual loss, polyuria and polydipsia, harboring an intracranial GCT. She presented initially to a neurosurgery clinic and then to an endocrine clinic, with a history of chronic worsening headache and recent onset visual blurring along with polyuria with polydipsia. On further inquiry, she was found to have primary amenorrhea, easy fatigability, and failure of development of secondary sexual characteristics. On examination the patient had bitemporal hemianopia with breast development at tanner stage II and pubic and axillary hair at tanner stage I. Her initial hormonal workup was suggestive of panhypopituitarism with diabetes insipidus. MRI pituitary showed a sellar mass with suprasellar extension, so an initial impression of a pituitary macroadenoma was made and the patient underwent trans-sphenoidal surgery. The histopathology was suggestive of lymphoid hyperplasia. Follow up MRI showed significant residual tumor and her vision and pituitary function did not recover. Neurosurgery was planned as second surgery, but we requested a second opinion of histopathology report and it was suggestive of a germinoma. She was then started on chemotherapy followed by radiotherapy, after which her tumor size reduced significantly, though she still required pituitary hormone replacement therapy.  Pituitary stalk lesions are rare and their diagnosis is challenging as different etiologies present clinically and radiologically in a similar manner with tissue diagnosis being the gold standard. Germinoma is a radiosensitive tumor. In our patient it took a long time to reach the correct diagnosis and late diagnosis resulted in permanent visual field defect and panhypopituitarism. This case report emphasizes that we should guide and educate our patients to seek medical advice early in the course of disease. We should also keep differential diagnosis in mind before referring the patient for surgery.

Presentation, Management, and Outcomes of Nonfunctioning Pituitary Adenomas: An Experience from a Developing Country.

Objective The goal of this study was to evaluate the presentation, management, and clinical outcome of nonfunctioning pituitary adenomas (NFPAs) in a tertiary care setup. Methods We conducted a retrospective review of patient records of 157 patients with the diagnosis of NFPA managed at Aga Khan University Hospital, a tertiary care hospital in Karachi, Pakistan from January 1, 2007, to December 31, 2017. We collected data on basic demographic characteristics, signs, and presenting symptoms, management, and outcomes. Data analysis was performed by using Stata, Version 12 (StataCorp LLC, College Station, TX). Results Most patients in the study were men (59%), and the mean age of the study population was 48 ± 14 years. The main presentations of NFPA were visual disturbance (77%) and headache (55%). In 78% of patients, the tumor was >1 cm on MRI. Most (87%) of patients underwent surgical resection, and of those, 93% received transsphenoidal surgery that was well tolerated. In the study population, 31% of patients had transient, 9% had permanent diabetes insipidus, and 25% developed hyponatremia. Of those in the study, 53% had low cortisol, 57% had hypothyroidism, and 27% needed sex hormone replacement after surgery. Residual tumor was confirmed in 43% of patients by postoperative MRI. Tumor recurrence and regrowth occurred in 17 patients and required repeat resection or radiosurgery. Conclusion In Pakistan, patients with NFPAs are more likely to present during the later stage, with larger adenoma and compressive symptoms compared to patients in developed countries. For the detection of residual disease and tumor recurrence, close screening and a multidisciplinary approach are needed after surgery.

Pre-operative serum TSH levels: A risk factor for advanced metastatic differentiated thyroid carcinoma.

BACKGROUND AND OBJECTIVE: As the thyroid cancer incidence is increasing, the search for its risk factor is becoming more important. Serum thyroid stimulating hormone (TSH) levels being a growth factor for normal thyroid tissue, is also considered as growth promotor of cancer cells. In our study we aimed for pre-operative serum TSH levels of Differentiated thyroid cancers (DTC) done before their first surgery and determined its association with advanced disease in terms of stage, multifocal disease, lymph node involvement and distant metastasis. METHODS: We have conducted a retrospective review of thyroid cancers from 1st January 2008 to 31st December 2017. Out of 281, 142 cases were included according to inclusion criteria. We noted the demographic details of participants, their histopathological diagnosis and serum TSH levels done before first surgery from the medical records. We calculated the stage of tumor through modified American Joint Committee (AJCC) staging system. RESULTS: Out of 147 participants, 89.4% had papillary carcinoma or its variants whereas 10.6% reported follicular carcinoma. The mean pre-op TSH level of the patients included was 2.04 ± 1.79. In addition to the descriptive analysis, the univariate regression analysis revealed that the association of serum TSH levels was found to be statistically insignificant with advanced stage of thyroid cancer, multifocal disease, lymph node metastasis and distant metastasis respectively. CONCLUSION: The serum TSH levels before surgery was not associated with poor prognosis of differentiated thyroid cancer with respect to higher staging, multifocal disease, lymphatic or distant metastasis.