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Insulinomas are rare neuroendocrine tumors with an annual incidence of four cases per million people in the general population. They have varied presentations making their diagnosis a challenging task necessitating a thorough patient assessment to ascertain early detection of this clinical entity by treating physicians. Insulinomas are characterized by the presence of Whipple's triad comprising of hypoglycemic symptoms, biochemical demonstration of hypoglycemia, and improvement of those symptoms after glucose administration. Biochemical detection of insulinoma by supervised 72-hour fasting test with plasma glucose, insulin, C-peptide, and proinsulin level measurements remains the gold standard of diagnosis. In this report, we present an interesting case of delayed diagnosis of pancreatic insulinoma. He was treated for more than six years as a psychiatric illness before receiving the correct diagnosis and treatment. Herein, a middle-aged man with a history of recurrent episodes of altered talk and confusion that resolved after eating something sweet. Biochemical investigations were suggestive of endogenous hyperinsulinemia. Pancreatic insulinoma was localized by a computed tomography scan. The patient underwent surgical resection of the tumor with complete resolution of his symptoms.
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Pituitary adenomas are one of the most common benign intracranial tumors, which are normally treated with surgery along with radiation therapy and medication such as dopamine agonist in prolactinoma. The aim of the present study was to evaluate the outcome of patients with pituitary macroadenoma who underwent radiation therapy. For the present retrospective study, a total of 75 patients with pituitary macroadenoma who received radiation therapy were included. Data was acquired from the electronic medical record system of the hospital. Mean ± standard deviation of the quantitative variables, such as age and sizes of the tumors, were reported. In addition, frequencies and percentages were presented for all categorical variables. To compare the frequency distribution in radiation therapy characteristics between functional and non-functional tumors, the χ2 test or Fisher's exact test was applied, where appropriate. Kaplan-Meier survival curve was drawn to assess the progression free survival proportion. P≤0.05 was considered to indicate a statistically significant difference. In the present study, all patients (n=75) with pituitary macroadenoma were treated with radiation therapy (RT). The mean age was 38.55±1.36 years and the majority of the patients were male (43; 57.3%). The mean tumor size was 3.84±1.43 cm. In total, 66.7% were non-functional tumors whereas 33.3% were functional tumors that produce hormones in excess [growth hormone (72%), prolactin (16%), both growth hormone and prolactin (8%) and adrenocorticotropic hormone (4%)]. The overall outcome was revealed to be 92% achieving local tumor control and 28% achieving biochemical control. Hypopituitarism (38.7%) and visual acuity deterioration (9.3%) were the most common complications observed following RT. The overall progression-free survival at 2 years was 92%. In conclusion, the data of the present study suggested that local tumor control in non-functional and functional pituitary macroadenoma can be well managed with RT. However, biochemical control to normalize hormones overproduction in functional pituitary macroadenoma was not as effective as local tumor control.
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Aim Prolactinoma, a prolactin (PRL) secreting functioning pituitary tumor, is the most common of all pituitary adenomas (PA) accounting for 40-60% and dopamine agonists (DA) are the cornerstone of treatment. The aim of this study was to review the clinical presentation, treatment modalities and therapeutic outcomes of patients with prolactinomas in the South Asia region. Methods This retrospective study was conducted in the Endocrinology Department of Shaukat Khanum Memorial Cancer Hospital and Research Centre from December 2011 till December 2019. Medical records were used to retrieve for patient's demographics, clinical features at diagnosis, PRL levels and size of prolactinoma on MRI at diagnosis and after start of dopamine agonists and outcome of medical management. Results A total of 107 patients were included in this study. Mean age at diagnosis was 35 (22-54) years for men and 32 (18-50) years for women and 66.4% (71) of the patients were females. Our study included 38 (35.5%) microadenoma, 50 (46.7%) macroadenoma and 19 (17.8%) giant adenomas. At presentation, the most common symptom among females was menstrual irregularity/amenorrhea seen in 73.2% of females and among males was visual disturbance (80.6%). A significant reduction in PRL levels was seen within six to 12 months of treatment. Mean PRL levels decreased from 3162.8 ng/ml to 1.52 ng/ml. A notable decrease in tumor size was seen with medical management, mean adenoma size decreased from 2.18 cm to 1.04 cm. With cabergoline (CAB) 83.3% biochemical cure was seen compared to bromocriptine (BRC) which has 60.4%. The radiological response rate in CAB and BRC groups was 65.45% and 60%, respectively. Complete resolution of adenoma was seen in 13 patients (nine were microadenoma, two macro and two giant adenomas). The prolactin level at diagnosis was positively correlated with maximum tumor diameter (r = 0.469, P = 0.001). Two patients developed cerebrospinal fluid (CSF) rhinorrhea and the defect was repaired in both patients. Median follow-up duration was 40 (12-288) months. Conclusion Clinical presentation and demographics of prolactinoma are the same in our region when compared to the rest of the world. Cabergoline is superior to bromocriptine in prolactin normalization and tumor shrinkage but still bromocriptine is being used in a significant number of patients in low-income countries as first-line due to its low cost.
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Background: Diabetes and cancer are the leading causes of mortality all over the world. Infectious diseases are more common and/or life-threatening in patients with diabetes. Cancer patients with diabetes are individuals that are more susceptible to the current COVID-19 pandemic. We investigated the clinical features of survivor and non-survivor COVID-19-infected cancer patients with diabetes. Patients and Methods: We did a retrospective study of 43 diabetic cancer patients with PCR-confirmed COVID-19 infection from Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan between March 03, 2020, and May 18, 2021. These patients either were discharged from the hospital or had died by Jun 16, 2021. Clinicopathological and radiological features were compared between survivors and non-survivors by fisher's exact test and chi-square test. Results: Forty-three diabetic cancer patients with SARS-CoV-2 infection were enrolled and the majority were males 26 (60.5%). The overall mean age was 61.67 ± 11.80. 39 (90.7%) had solid tumors and 3 (7.0%) had hematological malignancies. Fever (74.4%) and dyspnea (58.1%) were the most common symptoms. Complications were reported in 36 (83.7%) patients; during the course of the disease. Additionally, all the deceased patients (n=15) had acquired the complications. 11 (25.6%) patients were admitted to an intensive care unit (ICU). Furthermore, 29 (67.4%) out of 43 patients showed abnormal features in the radiological findings. We found significantly elevated levels of C-reactive protein (P=0.005), serum lactate (P=0.01), albumin (P=0.02), alkaline phosphate (P=0.03), and neutrophil count (P=0.04) in the non-survivors as compared to the survivors. Conclusion: Cancer patients with diabetes are a vulnerable population in the current pandemic. Identifying how diabetes in cancer patients affects the severity of SARS-CoV-2 infection is crucial for the clinical management of these patients. Rigorous scrutiny of clinicopathological features of COVID-19 infected cancer patients with diabetes especially values of C-reactive protein, lactate, albumin, alkaline phosphate, neutrophils, and regular monitoring of blood glucose levels may play a critical role in the outcome of the disease.
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The South Asian population is rapidly ageing and sarcopenia is likely to become a huge burden in this region if proper action is not taken in time. Several sarcopenia guidelines are available, from the western world and from East Asia. However, these guidelines are not fully relevant for the South Asian healthcare ecosystem. South Asia is ethnically, culturally, and phenotypically unique. Additionally, the region is seeing an increase in non-communicable lifestyle disease and obesity. Both these conditions can lead to sarcopenia. However, secondary sarcopenia and sarcopenic obesity are either not dealt with in detail or are missing in other guidelines. Hence, we present a consensus on the screening, diagnosis and management of sarcopenia, which addresses the gaps in the current guidelines. This South Asian consensus gives equal importance to muscle function, muscle strength, and muscle mass; provides cost-effective clinical and easy to implement solutions; highlights secondary sarcopenia and sarcopenic obesity; lists commonly used biomarkers; reminds us that osteo-arthro-muscular triad should be seen as a single entity to address sarcopenia; stresses on prevention over treatment; and prioritizes non-pharmacological over pharmacological management. As literature is scarce from this region, the authors call for more South Asian research guided interventions.
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Background Radioactive iodine (RAI) is the treatment of choice for most patients with primary hyperthyroidism. The most common etiologies of hyperthyroidism are Graves' disease (GD), toxic adenoma (TA), and toxic multinodular goiter (TMNG). A single dose of RAI is usually sufficient to cure hyperthyroidism. The aim of this study was to assess the effectiveness of RAI therapy for patients diagnosed with primary hyperthyroidism. Methods and materials Patients diagnosed with hyperthyroidism who received RAI therapy between 2008 and 2018 were included in the study. The data was acquired from the hospital's electronic medical record system. Following the RAI treatment, a cure was defined as the development of euthyroidism or hypothyroidism after a single fixed-dose without antithyroid medication within one year of RAI therapy. In addition, a simple logistics regression model was used to identify the prognostic factors that may lead to better outcomes. Results A total of 112 patients diagnosed with hyperthyroidism with a mean age of 47 ± 14 were included in this study. The majority of the patients were female, 79 (70.5%). Within one year of RAI therapy, 84 (75%) patients achieved a cure that is either hypothyroid or euthyroid status. RAI dose was higher in responsive patients (18.50 ± 4.10 millicurie [mCi] versus 16.50 ± 4.10 mCi) than in non-responsive patients. The mean RAI doses were 16.05 ± 2.99 mCi in GD, 19.81 ± 4.40 mCi in TMNG, and 20.50 ± 3.30 mCi in TA, with a statistically significant p-value of 0.001. In the univariable logistic regression model, RAI dose was a significant prognostic factor of the responsive group (OR: 1.15, CI [1.01-1.31], p-value 0.03). Conclusion Our data presented that RAI therapy is effective for primary hyperthyroidism. We achieved remission with a single fixed-dose in the majority of patients. Most of our patients were cured within three months of RAI therapy. In addition, the RAI dose was higher in the responsive group as compared to the non-responsive group.
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Adrenocortical carcinoma (ACC) is a rare and highly aggressive tumor with a poor prognosis. The literature on prognosis from low-income or low-middle-income countries is limited and scarce. This study aimed to determine the clinical and histopathological characteristics, recurrence-free survival (RFS), overall survival (OS), and the factors affecting ACC's prognosis. This was a retrospective study of patients that presented with ACC to the Shaukat Khanum Memorial Cancer & Research Center, Lahore, Pakistan, between January 2011 and May 2018. Information regarding demographics and clinical and histopathological variables were extracted and analyzed. Of the 25 subjects, 16 (64%) were female. The median age of the sample was 35 years (range; 21 - 72 years). Statistically significant associations were found between RFS and functional status of the tumor (p = 0.014), cortisol overproduction (p = 0.02), androgen excess (testosterone [p = 0.03] and dehydroepiandrosterone sulfate [DHEA SO4] [p = 0.004]), Ki-67 score (p = 0.03), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.01), and composite variable of disease (p = 0.004). The OS was found to have statistical associations with cortisol hypersecretion (p = 0.02), DHEA SO4 excess (p = 0.01), Modified Weis Score (p < 0.001), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.003), and composite variable of disease (p = 0.001). Linear regression (forward-type) analysis suggested that the functional status of the tumor and the disease recurrence index statistically predicted the variance in RFS and OS, respectively. Multiple clinical and histopathological variables appear to affect the prognosis of ACC. However, based on multivariable analysis, it appears that the functional status of the tumor and the composite variable of disease recurrence are predictors of RFS and OS, respectively.
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BACKGROUND: Bethesda category III and IV thyroid nodules fall in the indeterminate risk of malignancy category. These nodules have been a relatively elusive entity to manage as previous studies have shown a wide variation in malignancy rates in different regions and institutions across the world. However, data from the subcontinent with regards to this is scarce. AIM AND OBJECTIVE: This study aimed to determine the characteristics and malignancy rates of cytology proven Bethesda Category III and IV thyroid nodules and its association with clinical, histopathological and laboratory variables, in the regional population. METHOD: A retrospective search was performed on all patients with thyroid nodules who presented to this hospital, from January 2011 to September 2018. Patients who had cytology proven Bethesda category III and IV thyroid nodules that underwent surgery were included in the study. RESULTS: Malignancy in Bethesda Category III and Bethesda Category IV thyroid nodules was 29.6% and 47.1%, respectively. There was no significant association determined between malignancy rate and various clinical, histopathological, and radiological characteristics. CONCLUSION: The malignancy rates in Bethesda category III and IV thyroid nodules in this study are significantly higher than that initially suggested by the Bethesda consensus publication but is comparable to international data present.
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Disorder of sex development (DSD) is the term ascribed to a wide group of disorders presenting with congenital discord between chromosomal sex and phenotypic manifestation. Its incidence is 1 in 4500 births. 46 XX testicular DSD is a rare disorder characterized by the discordance between female karyotype and male phenotype. Its incidence is 1:20,000 to 25,000 male infants. It is further classified into SRY positive and SRY negative individuals, depending on the presence or absence of sex-determining region Y gene (SRY) on the X chromosome as a result of translocation. We are hereby reporting a rare case of de la Chapelle syndrome (SRY negative). A 30-year-old phenotypical male presented to us with complaints of primary infertility. He had had hypospadias during his childhood and underwent corrective surgery at the age of 18 years. For the previous 1.5 years, he had been complaining of decreased libido, difficulty in micturition, and presence of watery ejaculate. On examination, he had bilateral palpable testis with the testicular volume of 7 mL each, curved micropenis with chordee, and eccentric meatus with fistula. Semen analysis revealed azoospermia and hormonal profile was consistent with hypergonadotropic hypogonadism. His karyotyping turned out to be 46 XX chromosome without the SRY gene on polymerase chain reaction (PCR) array. He was medically treated with testosterone and underwent surgical correction of chordee. The SRY negative testicular 46 XX disorder is a rare expression and can be diagnosed at the time of birth with the presence of severe hypospadias, cryptorchidism, or ambiguous genitalia. All new-borns with these findings should undergo evaluation for the disorder of sexual development. Such individuals can never father a child and genetic counseling should be offered. Infertility is the main concern for such individuals which can be addressed by in vitro fertilization (IVF) with a sperm donor or adoption.
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Introduction: Prolactinomas are the most common pituitary adenomas. Medical therapy with dopamine agonists (DAs) is the mainstay of treatment and rarely requires surgical manipulation. Patients may rarely present with cerebrospinal fluid (CSF) rhinorrhoea after starting therapy with DA in case of massive or invasive prolactinomas. Case Description: We present a case of a 29-year-old lady with invasive prolactinoma who presented with CSF rhinorrhoea after a month of starting bromocriptine therapy with the development of meningitis and warranting early surgical repair. Practical Implications: Patients with macroprolactinoma should be closely monitored initially after starting on DA to avoid life-threatening complications.
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Background: The most common pituitary adenoma presentation is a visual field defect and inappropriate pituitary hormone secretion. The compression of the optic chiasm causes visual impairment. Large pituitary adenomas can rarely cause diplopia and ptosis secondary to adenoma's lateral extension into the cavernous sinus. Myasthenia gravis is an autoimmune disorder involving neuromuscular junctions. It is characterised by skeletal muscle fatigability, commonly involving extraocular muscles, face and limbs. It is estimated that 75% of myasthenia gravis patients present with ptosis and diplopia. The association of myasthenia gravis with pituitary adenoma is very rare. Case Description: A 30-year-old lady presented with headache, diplopia and ptosis of the left eye for 2 months. She was diagnosed with acromegaly secondary to pituitary adenoma. Ptosis is a rare presenting feature in pituitary adenoma. Her case was discussed in a multidisciplinary meeting, and the consensus was that her ptosis is likely secondary to pituitary adenoma, which was involving the left cavernous sinus. She underwent transsphenoidal resection of pituitary macroadenoma. Three weeks post-surgery, she developed bilateral ptosis, dysarthria and dysphonia, which was diagnosed as myasthenia gravis. Clinical Implications: Ptosis is a rare manifestation of pituitary adenoma. Nonetheless, pituitary tumour patients presenting with ptosis should be evaluated for the neuromuscular disorder. A high index of suspicion is required for early diagnosis and prompt treatment of myasthenia gravis.
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Introduction: Acromegaly is caused due to the unregulated and sustained overproduction of growth hormone (GH). The majority of the cases are caused by autonomous secretion of GH from anterior pituitary tumours. Nonetheless, in <1% of the cases, the cause of autonomous secretion is secondary to ectopic GH-releasing hormone (GHRH) production. Bronchial carcinoids are the most common cause of ectopic GHRH production. Case Description: A 32-year-old female presented to the clinic with a history of cough, haemoptysis and undocumented weight loss for 4 years. Initial workup showed a large right main stem endobronchial mass. Transbronchial biopsy of the mass revealed a Grade I neuroendocrine tumour (NET). During NET workup, a large sellar mass was incidentally found on cross-sectional imaging. The hormonal profile revealed markedly elevated insulin-like growth factor-1 (IGF-1) and mildly raised prolactin. The magnetic resonance imaging (MRI) brain study revealed pituitary macroadenoma measuring 2 cm × 1.2 cm × 1.5 cm. The patient underwent bronchial carcinoid tumour resection, which led to normalisation of serum IGF-1 and GH response to an oral glucose tolerance test. Subsequent MRI brain revealed complete resolution of previously noted sellar mass. Practical Implications: This case highlights the importance of differentiating acromegaly secondary to pituitary adenoma and ectopic acromegaly. This case emphasises the importance of keeping rare entities in the differential while assessing patients with pituitary macroadenoma.
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Primary amenorrhea is a serious medical condition. A thorough clinical assessment is necessary for a timely and correct diagnosis and management of this ailment to prevent long-term health and social problems. Turner's syndrome is considered one of the important causes of primary amenorrhea, with an incidence of one in 2,500 to one in 3,000 live-born girls. In this report, we present an interesting case involving multinodular goiter, hypothyroidism, and primary amenorrhea. A 24-year-old woman with a history of multinodular goiter and hypothyroidism attended an endocrine clinic with fine-needle aspiration cytology (FNAC) report of her bilateral thyroid nodules, which showed Bethesda category IV. She had a history of learning difficulties. During detailed history-taking, the patient also complained of primary amenorrhea. Clinical examination showed a lack of secondary sexual characters. Biochemical, imaging, and cytogenetic investigations were suggestive of absent ovaries and fallopian tubes, streaked uterus, hypergonadotropic hypogonadism, and X0 karyotyping. The learning objectives of this case report are as follows: firstly, in countries with a lack of awareness and limited health resources, patients may present with one of the manifestations of Turner's syndrome. Clinicians from all specialties should be aware of the clinical features of this relatively rare entity and should try to make the most of incidental clinical findings. Secondly, clinicians should be more vigilant and thorough in their clinical assessment of patients with learning difficulties to minimize the chances of missing a clinical diagnosis.
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Objective The aim of this study was to evaluate the demographic and clinical characteristics of patients with pheochromocytoma and determine the treatment outcome with overall survival rates of patients with pheochromocytoma. Methods A retrospective, cross-sectional study was performed on all the patients with histologically proven pheochromocytoma presenting to Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH & RC) Lahore, between August 2006 and July 2018. Clinical, biochemical and radiological data were collected at presentation, post-surgery, at discharge and till the last follow-up; data was retrieved from hospital records. Cure was defined as no evidence of disease biochemically, clinically, and structurally. Results This study included 29 patients, 69% were female. The three most common symptoms were abdominal pain (51.7%), hypertension (44.8%) and headache (41.4%). Most pheochromocytomas were sporadic (82.8%), all were adrenal gland tumors, and 89.7% were unilateral. All patients underwent adrenalectomy. Open adrenalectomy was performed in 25 patients whereas four underwent laparoscopic adrenalectomy. Fifteen patients experienced postoperative complications. The most frequently documented intraoperative complication was hypotension. Death occurred in two patients, one patient died of metastatic disease secondary to malignant pheochromocytoma and the other patient died from perioperative complications. Cure was documented biochemically and/or radiologically in 96.5% patients. Conclusions Abdominal pain was predominant presenting feature most likely due to large tumor size. Most patients presenting to SKMCH & RC, had large intra-abdominal tumors with high cure rate. Mortality was low despite high rate of perioperative complications.
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BACKGROUND: Thyroglobulin (Tg) measurement in patients with positive antithyroglobulin antibodies (anti-TgAbs) is not reliable. Tg measurement using liquid chromatography-tandem mass spectrometry (LC/MS) may be useful in this setting. METHODS: This is a retrospective study with the objective of determining the accuracy of Tg-LC/MS in patients with thyroid cancer with anti-TgAbs. All patients with follicular cell-derived thyroid cancer (TC) who had thyroglobulin measured using LC/MS assay from November 1, 2013, to November 7, 2014, were evaluated. The frequency of detectable Tg-LC/MS was evaluated, with a functional sensitivity (FS) of 0.5 ng/mL in patients with structural disease. Then performance of Tg-LC/MS versus Tg immunometric assay (IMA) was compared using either Immulite assay (Tg-1) with a FS of 0.9 ng/mL or Beckman assay (Tg-B) with a FS of 0.1 ng/mL in detecting structural disease in patients with positive anti-TgAbs. RESULTS: A total of 154 consecutive patients were included in this evaluation. Of these, 116 (75%) patients were positive for anti-TgAbs. In patients with structural disease and positive anti-TgAbs, Tg-LC/MS was undetectable in 43.7% of patients. Then the diagnostic accuracy for structural disease of Tg-LC/MS was compared with each Tg-IMA assay separately. In the 26 patients with positive anti-TgAbs where a Tg-I assay was used, the sensitivity and specificity for detecting structural disease were 33.3% and 88.2%, respectively, for the Tg-I assay, and 44.4% and 94.1%, respectively, for the Tg-LC/MS assay. In the 74 patients with positive anti-TgAbs where Tg-B was used, the sensitivity and specificity for detection of structural disease were 72.7% and 71.4%, respectively, for the Tg-B assay, and 62.6% and 93.7%, respectively, for the Tg-LC/MS assay. CONCLUSION: In patients with thyroid cancer with positive anti-TgAbs, Tg-LC/MS was frequently undetectable and was less sensitive for detecting disease than a Tg assay was with a functional sensitivity of 0.1 ng/mL. For patients with detectable Tg-LC/MS and anti-TgAbs, use of the assay for monitoring requires further prospective studies.
Subject(s)
Autoantibodies/analysis , Thyroglobulin/immunology , Thyroid Neoplasms/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Chromatography, Liquid , Female , Humans , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Tandem Mass Spectrometry , Young AdultABSTRACT
Objective. Thyroid disease has been reported among the endocrinopathies that can occur after treatment with ipilimumab. Graves' disease, however, has been rarely reported with this medication. Here we report a case of Graves' disease diagnosed after initiation of ipilimumab in a patient with melanoma. Methods. We present the clinical presentation and management course of this patient followed by a related literature review. Results. A 67-year-old male with metastatic melanoma was started on ipilimumab. He developed hyperthyroidism after two doses of ipilimumab. The cause of hyperthyroidism was determined to be Graves' disease. Ipilimumab was held and the patient was started on methimazole with return to euthyroid status. Ipilimumab was resumed and the patient continued methimazole during the course of ipilimumab therapy, with controlled hyperthyroidism. Restaging studies following four cycles of ipilimumab showed complete response in the lungs, with residual melanoma in the neck. The patient then underwent total thyroidectomy and left neck dissection as a definitive treatment for both hyperthyroidism and residual melanoma. Conclusion. Graves' disease can develop after starting ipilimumab and methimazole can be an effective treatment. For patients whose hyperthyroidism is well-controlled on methimazole, ipilimumab may be resumed with close monitoring.