Clonidine Stimulation Test: Is Single Best Time Point, Convenient Yet Efficacious?

CONTEXT: To find a single time point during clonidine stimulation test (CST), with highest diagnostic value to rule out growth hormone deficiency (GHD). SETTINGS AND DESIGN: This is a retrospective study of 79 CSTs carried out in a tertiary care center in India. MATERIALS AND METHODS: A cohort of 79 children with unexplained short stature was divided into two groups: GHD and non-GHD. Any one stimulated growth hormone (GH) level >10 ng/mL was used to rule out GHD. Diagnostic accuracy of not only single time points but also time points in pairs was calculated. STATISTICAL ANALYSIS: The data were analyzed using SPSS statistical software 22.0. Descriptive statistics were used for analyzing demographic data. Mode for time to peak GH was calculated in each group. The specificity and false positive rates at each time point as well as combined time points were determined. RESULTS: Assaying a single sample at 60 min after clonidine resulted in 20.5% false positive tests with specificity of 79.5%. Addition of the 90 min sample increased specificity to 92.3%. CONCLUSION: The 60 min sample after clonidine stimulation was the best single sample to rule out GH deficiency. Combined sampling at 60 min + 90 min is economical and less cumbersome, with minimal compromise on the specificity.

Phenotype-genotype spectrum of AAA syndrome from Western India and systematic review of literature.

OBJECTIVE: To study genotype-phenotype spectrum of triple A syndrome (TAS). METHODS: Retrospective chart analysis of Indian TAS patients (cohort 1, n = 8) and review of genotyped TAS cases reported in world literature (cohort 2, n = 133, 68 publications). RESULTS: Median age at presentation was 4.75 years (range: 4-10) and 5 years (range: 1-42) for cohorts 1 and 2, respectively. Alacrima, adrenal insufficiency (AI), achalasia and neurological dysfunction (ND) were seen in 8/8, 8/8, 7/8 and 4/8 patients in cohort 1, and in 99, 91, 93 and 79% patients in cohort 2, respectively. In both cohorts, alacrima was present since birth while AI and achalasia manifested before ND. Mineralocorticoid deficiency (MC) was uncommon (absent in cohort 1, 12.5% in cohort 2). In cohort 1, splice-site mutation in exon 1 (p.G14Vfs*45) was commonest, followed by a deletion in exon 8 (p.S255Vfs*36). Out of 65 mutations in cohort 2, 14 were recurrent and five exhibited regional clustering. AI was more prevalent, more often a presenting feature, and was diagnosed at younger age in T group (those with truncating mutations) as compared to NT (non-truncating mutations) group. ND was more prevalent, more common a presenting feature, with later age at onset in NT as compared to T group. CONCLUSION: Clinical profile of our patients is similar to that of patients worldwide. Alacrima is the earliest and most consistent finding. MC deficiency is uncommon. Some recurrent mutations show regional clustering. p.G14Vfs*45 and p.S255Vfs*36 account for majority of AAAS mutations in our cohort. Phenotype of T group differs from that of NT group and merits future research.

Comparison of 68Ga-DOTANOC PET/CT and contrast-enhanced CT in localisation of tumours in ectopic ACTH syndrome.

BACKGROUND: 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 (68)Ga-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 (68)Ga-DOTANOC PET/CT were reported (blinded) by an experienced radiologist and a nuclear medicine physician, respectively. The performance of CECT and (68)Ga-DOTANOC PET/CT was compared. RESULTS: 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)). (68)Ga-DOTANOC PET/CT was able to identify 9 out of 13 lesions (sensitivity 69.2%) and reported no false-positive lesions (PPV 100%). CONCLUSION: CECT remains the first-line investigation in localisation of EAS. The contrast enhancement pattern on CECT can further aid in characterisation of the lesions. (68)Ga-DOTANOC PET/CT can be added to CECT, to enhance positive prediction of the suggestive lesions.

HIGH-PRECISION CONFORMAL FRACTIONATED RADIOTHERAPY IS EFFECTIVE IN ACHIEVING REMISSION IN PATIENTS WITH ACROMEGALY AFTER FAILED TRANSSPHENOIDAL SURGERY.

OBJECTIVE: Variable efficacy of pituitary radiotherapy in acromegaly is reported. Here we sought to assess the efficacy of high-precision conformal fractionated radiotherapy (CRT) in patients with acromegaly after failed TSS. METHODS: A retrospective analysis was conducted a in tertiary care referral center between 1999 to 2013 on 36 acromegaly patients (M: 16, F: 20; median age: 36.0 years) with macroadenoma and mean growth hormone (GH) and insulin-like growth factor-1 (IGF1) upper limits of normal (ULN) of 15.9 ± 14.3 ng/mL and 1.74 ± 0.43, respectively. The cohort was divided into 2 groups: 30 patients (M: 13, F: 17) who were medical treatment naïve, and 6 patients (M: 3, F: 3) who received medical treatment after CRT. RESULTS: Normalization of GH (fasting GH <1 ng/mL), normalization of IGF1 (ULN <1), and remission (normalization of GH and IGF1) were achieved in 20 (55%), 23 (63%) and 20 (55%) patients, respectively. The mean time required to achieve remission was 63 ± 33.4 months. Follow-up duration was the only predictor of achieving remission. GH level declined exponentially by 65% and 89% at 2 and 5 years, respectively. New onset hypopituitarism was noted in 33% of patients. Tumor control was achieved in 100% of patients. In groups 1 and 2, 18 (60%) and 2 (33.3%) achieved remission post-CRT, and the mean times required to achieve remission were 58.6 ± 30.7 months and 102 ± 42.4 months, respectively. CONCLUSION: High-precision CRT is an effective modality to achieve remission in patients with acromegaly after failed TSS.

Gender differences in macroprolactinomas: a single centre experience.

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.