Macroprolactinomas are the most common functional pituitary tumours. Hypotheses proposed to explain predominance of large tumours in males are: i) diagnostic delay, as hyperprolactinaemia remains under recognised in males and ii) gender-specific difference in tumour proliferation indices. Our study objectives are to compare gender differences in clinical, biochemical, radiological features, management outcomes and cabergoline responsiveness in macroprolactinomas. Drug resistance was defined as failure to achieve prolactin normalisation and >50% reduction in tumour volume with cabergoline (3.5 mg/week dose for minimum 6 months duration). The baseline characteristics of 100 patients (56 females and 44 males) with macroprolactinoma were analysed. Drug responsiveness was analysed in 88 treatment naive patients, excluding 12 post-primary trans-sphenoidal surgery cases. We found that females (30.29±10.39 years) presented at younger mean age than males (35.23±9.91 years) (P<0.01). The most common presenting symptom was hypogonadism (oligo-amenorrhoea/infertility) in females (96.15%) and symptoms of mass effect (headache and visual field defects) in males (93.18%). Baseline mean prolactin levels were significantly lower in females (3094.36±6863.01 ng/ml) than males (7927.07±16 748.1 ng/ml) (P<0.001). Maximal tumour dimension in females (2.49±1.48 cm) was smaller than males (3.93±1.53 cm) (P<0.001). In 88 treatment naïve patients, 27.77% females and 35.29% males had resistant tumours (P=0.48). On subgrouping as per maximum tumour dimension (1.1–2 cm, 2.1–4 cm and >4 cm), gender difference in response rate was insignificant. In conclusion, macroprolactinomas are equally prevalent in both sexes. Macroprolactinomas in males predominantly present with symptoms of mass effects, as against females who present with symptoms of hypogonadism. Males harbor larger tumours but are equally cabergoline responsive as those in females.
Shruti Khare, Anurag R Lila, Hiren Patt, Chaitanya Yerawar, Manjunath Goroshi, Tushar Bandgar, and Nalini S Shah
Sweta Budyal, Swati Sachin Jadhav, Rajeev Kasaliwal, Hiren Patt, Shruti Khare, Vyankatesh Shivane, Anurag R Lila, Tushar Bandgar, and Nalini S Shah
Variable prevalence of subclinical Cushing's syndrome (SCS) has been reported in patients with type 2 diabetes mellitus (T2DM), making the need for screening in this population uncertain. It is unknown if this variability is solely due to study-related methodological differences or a reflection of true differences in ethnic predisposition. The objective of this study is to explore the prevalence of SCS in Asian Indian patients with T2DM. In this prospective single center study conducted in a tertiary care referral center, 993 T2DM outpatients without any discriminatory clinical features (easy bruising, facial plethora, proximal muscle weakness, and/or striae) of hypercortisolism underwent an overnight 1 mg dexamethasone suppression test (ODST). ODST serum cortisol ≥1.8 μg/dl was considered positive, and those with positive results were subjected to 48 h, 2 mg/day low dose DST (LDDST). A stepwise evaluation for endogenous hypercortisolism was planned for patients with LDDST serum cortisol ≥1.8 μg/dl. Patients with positive ODST and negative LDDST were followed up clinically and re-evaluated a year later for the development of clinically evident Cushing's syndrome (CS). In this largest single center study reported to date, we found 37 out of 993 (3.72%) patients had ODST serum cortisol ≥1.8 μg/dl. None of them had LDDST cortisol ≥1.8 μg/dl, nor did they develop clinically evident CS over a follow-up period of 1 year. Specificity of ODST for screening of CS was 96.3% in our cohort. None of the T2DM outpatients in our cohort had SCS, hence cautioning against routine biochemical screening for SCS in this cohort. We suggest screening be based on clinical suspicion only.
Majunath R Goroshi, Swati S Jadhav, Anurag R Lila, Rajeev Kasaliwal, Shruti Khare, Chaitanya G Yerawar, Priya Hira, Uday Phadke, Hina Shah, Vikram R Lele, Gaurav Malhotra, Tushar Bandgar, and Nalini S Shah
Localising ectopic adrenocorticotrophic hormone (ACTH) syndrome (EAS) tumour source is challenging. Somatostatin receptor-based PET imaging has shown promising results, but the data is limited to case reports and small case series. We reviewed here the performance of 68Ga-DOTANOC positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT (CECT) in our cohort of 12 consecutive EAS patients.
Materials and methods
Retrospective data analysis of 12 consecutive patients of EAS presenting to a single tertiary care centre in a period between January 2013 and December 2014 was done. CECT and 68Ga-DOTANOC PET/CT were reported (blinded) by an experienced radiologist and a nuclear medicine physician, respectively. The performance of CECT and 68Ga-DOTANOC PET/CT was compared.
Tumours could be localised in 11 out of 12 patients at initial presentation (overt cases), whereas in one patient, tumour remained occult. Thirteen lesions were identified in 11 patients as EAS source (true positives). CECT localised 12 out of these 13 lesions (sensitivity 92.3%) and identified five false-positive lesions (positive predictive value (PPV) 70.5%). Compared with false-positive lesions, true-positive lesions had greater mean contrast enhancement at 60s (33.2 vs 5.6 Hounsfield units (HU)). 68Ga-DOTANOC PET/CT was able to identify 9 out of 13 lesions (sensitivity 69.2%) and reported no false-positive lesions (PPV 100%).
CECT remains the first-line investigation in localisation of EAS. The contrast enhancement pattern on CECT can further aid in characterisation of the lesions. 68Ga-DOTANOC PET/CT can be added to CECT, to enhance positive prediction of the suggestive lesions.
Manjeetkaur Sehemby, Prachi Bansal, Vijaya Sarathi, Ashwini Kolhe, Kanchan Kothari, Swati Jadhav-Ramteke, Anurag R Lila, Tushar Bandgar, and Nalini S Shah
Literature on virilising ovarian tumors (VOTs) is limited to case reports and series reporting single pathological type. We have analyzed the clinical, hormonal, radiological, histological, management and outcome data of VOT. This retrospective study was conducted at a tertiary health care center from Western India. Consecutive patients with VOT presenting to our endocrine center between 2002 and 2017 were included. Our study included 13 patients of VOT. Out of 13 patients, two were postmenopausal. All patients in the reproductive age group had secondary amenorrhea except one who presented with primary amenorrhea. Modified F and G score (mFG) at presentation was 24 ± 4.3 and all patients had severe hirsutism (mFG ≥15). Change in voice (n = 11) and clitoromegaly (n = 7) were the other most common virilising symptoms. Duration of symptoms varied from 4 to 48 months. Median serum total testosterone level at presentation was 5.6 ng/mL with severe hyperandrogenemia (serum testosterone ≥2 ng/mL) but unsuppressed gonadotropins in all patients. Transabdominal ultrasonography (TAS) detected VOT in all except one. Ten patients underwent unilateral salpingo-oophorectomy whereas three patients (peri- or postmenopausal) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Seven patients had Sertoli Leydig cell tumor, three had steroid cell tumor and two had Leydig cell tumor and one had miscellaneous sex cord stromal tumor. All patients had normalization of serum testosterone after tumor excision. In conclusion, VOTs present with severe hyperandrogenism and hyperandrogenemia. Sertoli Leydig cell tumor is the most common histological subtype. Surgery is the treatment of choice with good surgical outcome.
Manjunath Goroshi, Swati S Jadhav, Vijaya Sarathi, Anurag R Lila, Virendra A Patil, Ravikumar Shah, Priya Hira, Rajaram Sharma, Shettepppa Goroshi, Gwendolyn Fernandes, Amey Rojekar, Abhay Dalvi, Ganesh Bakshi, Gagan Prakash, Nalini S Shah, and Tushar R Bandgar
Rationale and introduction
To evaluate the computerised tomography (CT) characteristics of phaeochromocytoma (PCC) that differentiate them from other non-benign adrenal masses such as adrenocortical carcinoma (ACC), primary adrenal lymphoma (PAL) and adrenal metastases (AM).
This retrospective study was conducted at a tertiary health care institute from Western India. Patients presented between January 2013 and August 2016 with histological diagnosis of PCC or other non-benign adrenal mass having adequate reviewable imaging data comprising all four CECT phases were included.
The study cohort consisted of 72 adrenal masses from 66 patients (33 PCC, 22 ACC, 4 PAL, 13 AM). Unlike other masses, majority of PCC (25/33) showed peak enhancement in early arterial phase (EAP). PCC had significantly higher attenuation in EAP and early venous phase (EVP), and higher calculated percentage arterial enhancement (PAE) and percentage venous enhancement (PVE) than other adrenal masses (P < 0.001). For diagnosis of PCC with 100% specificity, PAE value ≥100% and EAP attenuation ≥100 HU had 78.8 and 63.6% sensitivity respectively. ACC were significantly larger in size as compared to PCC and metastasis. The adreniform shape was exclusively found in PAL (two out of four) and AM (4 out of 13). None of the enhancement, wash-in or washout characteristics were discriminatory among ACC, PAL and AM.
Peak enhancement in EAP, PAE value ≥100% and EAP attenuation ≥100 HU differentiate PCC from other malignant adrenal masses with high specificity.
Ravikumar Shah, Anurag R Lila, Ramteke-Swati Jadhav, Virendra Patil, Abhishek Mahajan, Sushil Sonawane, Puja Thadani, Anil Dcruz, Prathamesh Pai, Munita Bal, Subhada Kane, Nalini Shah, and Tushar Bandgar
Tumor-induced osteomalacia in the head and neck region remains a challenging diagnosis to manage. Literature pertaining to management and outcome details remains sparse. We describe two cohorts: cohort 1 included seven patients from a single center in Western India with tumors located in paranasal sinuses (n = 3), intracranial (n = 2) and maxilla (n = 2). The unique features from our series is the management of persistent disease with radiation therapy (n = 2) and peptide receptor radionuclide therapy (PRRT) (n = 1). Cohort two has 163 patients identified from 109 publications for systematic review. Paranasal sinuses, mandible, intracranial disease, maxilla and oral cavity, in descending order, are reportedly common tumor sites. Within this cohort, mean age was 46 ± 14 years at presentation with 44.1% having local symptoms. Duration of symptoms varied from 1 to 240 months. Pre-surgery mean serum phosphorus was 1.4 ± 0.4 mg/dL and median FGF-23 levels were 3.6 (IQR:1.8–6.8) times of normal upper limit of normal. Majority (97.5%) were managed primarily with surgical excision; however, primary radiotherapy (n = 2) and surgery combined with radiotherapy (n = 2) were also reported. Twenty patients had persistent disease while nine patients had recurrence, more commonly noted with intracranial and oral cavity tumors. Surgery was the most common second mode of treatment employed succeeded by radiotherapy. Four patients had metastatic disease. The most common histopathological diagnosis reported is PMT mixed connective tissue, while the newer terminology ‘PMT mixed epithelial and connective tissue type’ has been described in 15 patients.
Sanjeet Kumar Jaiswal, Vijaya Sarathi, Saba Samad Memon, Robin Garg, Gaurav Malhotra, Priyanka Verma, Ravikumar Shah, Manjeet Kaur Sehemby, Virendra A Patil, Swati Jadhav, Anurag Ranjan Lila, Nalini S Shah, and Tushar R Bandgar
177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) is a promising therapy for metastatic and/or inoperable pheochromocytoma and paraganglioma (PPGL). We aim to evaluate the efficacy and safety of and identify predictors of response to 177Lu-DOTATATE therapy in metastatic and/or inoperable PPGL.
This retrospective study involved 15 patients of metastatic or unresectable PPGL, who received 177Lu-DOTATATE PRRT therapy. Clinical, biochemical (plasma-free normetanephrine), and radiological (anatomical and functional) responses were compared before and after the last therapy.
A total of 15 patients (4 PCC, 4 sPGL, 5 HNPGL, 1 PCC + sPGL, 1 HNPGL + sPGL) were included. The median duration of follow up was 27 (range: 11–62) months from the start of PRRT. Based on the RECIST (1.1) criteria, progressive disease was seen in three (20%), stable disease in eight (53%), partial response in one (7%), and minor response in three (20%) and controlled disease in 12 (80%). On linear regression analysis the presence of PGL (P= 0.044) and baseline SUVmax >21 (P < 0.0001) were significant positive predictors of early response to PRRT. Encouraging safety profiles were noted with no long term nephrotoxicity and hematotoxicity.
177Lu-DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic/inoperable PPGL. Although it is not prudent to withhold PRRT in metastatic PPGL with baseline SUVmax < 21, baseline SUVmax >21 can be used to predict early response to PRRT.