Coexistent Pituitary Adenoma with Rathke's Cleft Cyst: A Case Series.

Objective: Co existent pituitary adenoma and Rathke's cleft cyst (RCC) is a rare entity. Purpose of this study is to describe the clinical presentation, imaging findings, and management of patients with this combination. Methods: Retrospective review of records from a single tertiary care center for a period of three years [2009-2012]. Results: Out of the total 284 pituitary adenoma patients in the study period, there were four patients one each of Cushing's disease, acromegaly, prolactinoma and non-secretory pituitary adenoma with coexisting RCC in all. Three of these were diagnosed to have coexisting RCC in preoperative MRI. All of them underwent transphenoidal excision of the lesions. Histopathology confirmed the collision sellar lesions in all four. Conclusions: It is difficult to diagnose coexisting RCC preoperatively due to variable size, position and signal intensity. However when a nonenhancing cyst is incidentally detected by MRI in a patient with pituitary adenoma, the possibility of a coexisting RCC should be considered.

Spectrum of phenotype and genotype of congenital isolated hypogonadotropic hypogonadism in Asian Indians.

BACKGROUND: Congenital isolated hypogonadotropic hypogonadism (IHH) is caused due to defect in GnRH neuronal development, migration and action. Although genetic aetiology of IHH is increasingly being studied, Asian Indian data on phenotypic spectrum and genetic basis are scarce. OBJECTIVE: To investigate the phenotypic and genotypic spectrum of IHH in Asian Indian subjects. DESIGN, SETTING AND SUBJECTS: A cohort of 135 IHH probands were characterized phenotypically for reproductive and nonreproductive features and screened for rare sequence variations (RSVs) in five genes KAL1, FGFR1, FGF8, GNRHR and KISS1R. RESULT: Of 135 probands [56 normosmic IHH (nIHH) and 79 Kallmann syndrome (KS)], 20 were familial cases. KS group had more male dominance (M:F ratio of 8:1) as compared to nIHH group (M:F ratio of 1·5:1). Complete absence of puberty was more prevalent in KS probands (81% in KS vs 46% in nIHH). The prevalence of MRI abnormalities was more in anosmic group (92·8%) as compared to hyposmic (37·5%) and normosmic groups (15·4%). No particular nonreproductive phenotypic predominance was seen in any group. Genotyping revealed rare sequence variation (RSV) detection rate of 15·5% in five genes studied: (KAL1 - 4·4%, FGFR1 - 4·4%, GNRHR - 6·7%, oligogenicity - 1·5%). Prevalence of RSV was more common in familial cases (35%) as compared to sporadic (12·2%). GNRHR RSV p.C279Y (not reported in patients of ethnicities other than south Asians) was recurring in four unrelated patients. CONCLUSION: In our cohort, 60% were KS with majority of males and a severe reproductive phenotype as against nIHH. Contribution of the genetic burden for the five genes studied was 15·5%. RSV p.C279Y in GNRHR may have a founder effect originating from south Asia. This study provides a model for molecular and phenotypic representation of Asian Indian subjects with IHH.

Primary (autoimmune) hypophysitis: a single centre experience.

BACKGROUND: Autoimmune hypophysitis (AH) is a rare autoimmune inflammatory disorder of pituitary gland. OBJECTIVE: To analyse clinical, hormonal, radiological features and management outcomes of AH. DESIGN: Retrospective analysis of patients with primary hypophysitis (where secondary causes of hypophysitis were ruled out) was carried out from 2006 to 2012. AH emerged as the most plausible aetiology and the diagnosis of exclusion. RESULTS: Twenty-four patients with AH (21 females and 3 males) were evaluated. They presented with symptoms of expanding sellar mass (83.3%), symptoms of anterior pituitary hormone deficiencies (58.3%), and diabetes insipidus (16.7%). The anterior pituitary hormonal axes affected were cortisol (75%), thyroid (58.33%) and gonadotropin (50%). All had sellar mass on magnetic resonance imaging, which was symmetrical (91.7%) and homogenously enhancing (91.7%). Stalk thickening, suprasellar extension, loss of posterior pituitary hyperintensity and parasellar T2 dark sign were seen in 87.5, 87.5, 71.5, and 50% respectively. In addition to hormone replacement, five (20.83%) patients underwent trans-sphenoidal surgery, fifteen (62.5%) were watchfully monitored, while four cases (16.67%) received steroid pulse therapy. On follow up imaging, the sellar mass regressed in all, while, stalk thickening was persistent in 13/19 (68.4%) non-operated patients at median follow up of 1 year. Pituitary hormone axis recovery was seen in 10 (41.67%) and was seen in cortisol 10/18 (55.5%) followed by gonadotropin 5/12 (41.67%) axis. CONCLUSION: Characteristic radiology helps in diagnosis of AH even without tissue diagnosis. Non-operative treatment is the preferred treatment modality. Steroid pulse therapy potentially improves pituitary axis recovery.

The performance and reproducibility of late-night salivary cortisol estimation by enzyme immunoassay for screening Cushing disease.

OBJECTIVE: Our study aimed to establish a local reference range for late-night salivary cortisol (LNSC) using enzyme immunoassay (EIA) and to study the intra-individual reproducibility of LNSC. METHODS: Prospective study involving 30 healthy subjects (HS) with body mass index (BMI) <25 kg/m2, 37 obese/overweight subjects (OS) with BMI >25 kg/m2 and 28 patients with Cushing disease (CD). Salivary sampling was performed on 2 consecutive nights and assayed by EIA. The reference range was established using LNSC values of HS, and receiver operating characteristic (ROC) curves were used to determine diagnostic cutoffs. RESULTS: The mean LNSC level of CD was significantly higher than HS and OS (CD: 16.96 ± 9.11 nmol/L, HS: 1.30 ± 0.95 nmol/L, and OS 1.21 ± 0.78 nmol/L). A cutoff of 2.92 nmol/L differentiated CD from HS with 100% sensitivity and 96.7 % specificity, and a cutoff of 5.04 nmol/L yielded a specificity of 100% with a sensitivity of 96.4% to distinguish CD from OS. There was more intra-individual variability in HS (55%) than in CD (49%) and OS (22%). There was no difference in the sensitivity and specificity derived from the ROCs using day 1 values or the higher of the 2 LNSCs. CONCLUSIONS: In our cohort, we found that LNSC assayed by EIA showed good sensitivity and specificity to screen patients suspected to have CD. Although intra-individual variability was significant, it did not hamper the diagnostic performance of the test.

Clinical, biochemical and imaging characteristics of Cushing's macroadenomas and their long-term treatment outcome.

OBJECTIVE: Cushing's macroadenoma as a cause of Cushing's disease is less common than microadenoma. The data on nature and behaviour of Cushing's macroadenoma are limited to a few case series. We studied clinical, biochemical and imaging characteristics of macroadenoma and their long-term treatment outcomes. METHOD: Retrospective analysis of 40 patients with macroadenoma managed at our centre from 1997 to 2013. RESULTS: Of 40 patients, there were 15 (37·5%) males and 25 (62·5%) females. Mean age at presentation was 26·7 ± 9·3 years. Visual field defects and/or cranial nerve palsies were found in 15 cases at presentation. Mean maximum tumour dimension was 20·83 ± 10·74 mm, and parasellar extension was seen in 25 (62·5%) patients. Plasma ACTH/maximum tumour dimension and 8 am serum cortisol/maximum tumour dimension decreased with increasing tumour size. Sixteen patients (40%) had remission (4: immediate, 12: delayed) after first transsphenoidal surgery (TSS). Larger tumour size and parasellar extension were predictors of failure to achieve remission. Four patients relapsed; noticeably all of them had delayed remission. Among the persistent and relapsed cases, second TSS was successful in two of eight patients, whereas 11 of 16 patients achieved remission after a mean duration of 12·14 ± 8·41 months postradiotherapy. CONCLUSION: Younger age at presentation and larger tumour size compared with previous series were distinctive features of our series. Large tumour size and parasellar extension were negative predictors of surgical remission. Delayed remission was seen in significant proportion of patients, but one-third later relapsed. Radiotherapy was an effective second-line treatment modality.

18F-FDG PET as a monitoring tool to assess treatment response in bilateral adrenal histoplasmosis.

A 60-year-old woman with clinical and biochemical features suggestive of adrenal insufficiency was found to have bilateral adrenal masses on CT scan and was subjected to F-FDG PET scan. The scan showed hypermetabolic mediastinal nodes in addition to intense tracer uptake in bilateral adrenal masses. CT-guided adrenal biopsy grew Histoplasma capsulatum on Sabouraud dextrose agar culture. A second F-FDG PET scan after 6 months of appropriate antifungal therapy showed a significant decrease in intensity of uptake consistent with the clinical outcome.

Radiofrequency ablation, an effective modality of treatment in tumor-induced osteomalacia: a case series of three patients.

CONTEXT: Tumor-induced osteomalacia is curable if the tumors can be totally excised. However, when the tumors are present in locations that make surgery disproportionately risky, the need for less invasive strategies like radiofrequency ablation (RFA) is realized. PATIENTS AND METHODS: We describe three patients with suspected tumor-induced osteomalacia who were treated in our department between 2006 and 2013 with tumors in surgically difficult locations and were subjected to single or multiple sessions of RFA. The response was documented in terms of symptomatic improvement, phosphorus normalization, and follow-up (99m)Technitium-labelled hydrazinonicotinyl-Tyr3-octreotide ((99m)Tc HYNIC TOC) scan. RESULTS: Two of the three individuals, patient A (with a 1.5 × 1.2-cm lesion in the head of the right femur) and patient B (with a 1.3 × 1.2-cm lesion on the endosteal surface of the shaft of the left femur), achieved complete remission with single sessions of RFA. Three months after the procedure, (99m)Tc HYNIC TOC scans revealed the absence of uptake at the previous sites, corroborating with the clinical improvement and phosphorus normalization. Patient C had a large 5.6 × 6.5-cm complex lesion in the lower end of the left femur with irregular margins, loculations, and bone grafts placed in previous surgery. He failed to achieve remission after multiple sessions of RFA due to the complex nature of the lesion, although the tumor burden was reduced significantly as documented on serial (99m)Tc HYNIC TOC scans. CONCLUSIONS: Although surgery remains the treatment of choice, RFA could be an effective, less invasive, and safe modality of treatment in judiciously selected patients.

Pheochromocytoma and tetralogy of Fallot: a rare but potentially dangerous combination.

OBJECTIVE: To describe a case of pheochromocytoma (PHEO) with tetralogy of Fallot (TOF) and discuss the difficulties encountered during the management of this patient, with a review of the literature. METHODS: We report the clinical course, imaging, and management issues of our patient and review relevant literature. RESULTS: A 14-year-old female who was known to have TOF presented with classical paroxysmal symptoms and worsening dyspnea. She was diagnosed as having epinephrine-secreting PHEO based on biochemical, radiologic, and functional imaging. She was treated with an α-1 blocker for control of paroxysms but developed severe cyanotic spells. She required addition of a calcium-channel blocker for control of the paroxysms and underwent successful cardiac repair. CONCLUSION: Treatment of the combination of cyanotic congenital heart disease (CCHD) and PHEO requires an individualized and multidisciplinary approach with judicious use of available medications. This is the first case of uncorrected TOF and epinephrine-secreting PHEO. Our case also reiterates the need for further studies to better understand the pathophysiologic link between PHEO/paraganglioma and CCHD.

An objective olfactory evaluation and its correlation with magnetic resonance imaging findings in Asian Indian patients with idiopathic hypogonadotropic hypogonadism.

OBJECTIVE: Idiopathic hypogonadotropic hypogonadism (IHH) can be associated with subnormal sense of smell. The objective of our study was to determine if there is a correlation between the olfactory phenotype (clinical smell test) of IHH patients and structural abnormalities in the olfactory apparatus on magnetic resonance imaging (MRI). METHODS: This was a single-center prospective case control study. Forty-one IHH patients underwent a brief University of Pennsylvania Smell Identification Test (UPSIT) and an MRI of the olfactory apparatus. The size of the olfactory sulcus and bulb were quantified and compared with the normative data of 40 controls. Agreement between UPSIT and MRI results was assessed using the kappa index. RESULTS: MRI showed that the olfactory apparatus was normal in 17 patients, hypoplastic in 14, and aplastic in 10. All 13 patients who complained of anosmia and 12 of 28 patients who reported normosmia had a low UPSIT score. Thus, 25 patients had Kallmann syndrome (KS) and 16 were normosmic IHH (nIHH). MRI revealed abnormalities in 68% of KS and 37.5% of nIHH patients. The MRI abnormalities in KS patients were aplasia (56%) and hypoplasia (44%). All 6 nIHH patients with abnormal MRI had hypoplasia. A significant positive correlation (r = 0.61; P<.01) between olfactory bulb volume (from MRI) and smell-test score was found, and there was good agreement (kappa index, 0.72) between anosmia and the presence of an aplastic olfactory apparatus. CONCLUSION: Self-reporting of the sense of smell significantly underestimates olfactory phenotype; hence, we recommend an objective smell test to distinguish KS from nIHH. Olfactory phenotype correlates well with MRI quantification of the olfactory apparatus in IHH.

Ectopic ACTH-secreting syndrome: a single-center experience.

OBJECTIVE: Ectopic adrenocorticotropic hormone (ACTH)-secreting syndrome (EAS) is a rare cause of ACTH-dependent endogenous hypercortisolism. The objective of this study was to analyze clinical, biochemical, and imaging characteristics; management strategies; and outcomes of EAS patients. METHOD: We screened the records (1993-2012) of ACTH-dependent endogenous hypercortisolism cases managed at a tertiary care center. RESULTS: Of the 218 patients, 17 were diagnosed with EAS. The median 8:00 AM serum cortisol was 36 µg/dL (11.4-82.7 µg/dL), and the median basal plasma ACTH was 156 pg/mL (53.5-468 pg/mL). Notably, ACTH levels below 100 pg/mL were found in 4 patients. Suspicious microadenoma was found on magnetic resonance imaging (MRI) of the pituitary in 5 patients, and all of them underwent transsphenoidal surgery (TSS). Inferior petrosal sinus sampling (IPSS) was performed in 8 patients, and the results were suggestive of a peripheral source in all 8. Computed tomography (CT) localized the lesion in 15/17 patients. In 2 patients with negative CTs, gallium DOTATATE positron emission tomography (PET) scans localized the lesion. Despite difficulties localizing bronchial carcinoids, the cure rate was high (72%). In contrast, thymic carcinoids were easily localized but had poor outcomes. CONCLUSION: EAS cannot be ruled out on the basis of marginally elevated ACTH. In cases with an equivocal MRI pituitary finding, prior IPSS can help avoid unnecessary TSS. CT is a useful modality for localization of an ectopic source. Functional imaging may help in cases where anatomical imaging fails.

Hyperphagic short stature: A case report and review of literature.

A 5½-year-old adopted girl was referred to us in view of short stature. After ruling out systemic illness, she was evaluated for growth hormone deficiency (GHD) by stimulation tests. The peak value was 3.47 ng/ml. She was then started on growth hormone (GH). At the end of 6 months of GH therapy, her height velocity was only 3 cm/year. There was a lack of attachment between the mother and the child. She had history of hyperphagia, stealing, and hoarding food. Psychiatry consultation confirmed that the child had appetite disorder, and hence was diagnosed as hyperphagic short stature (HSS). The girl and her parents are undergoing psychiatric therapy for the same. Psychosocial dwarfism seems to originate from serious disturbances in the mother-child relationship. These children mimic patients with GHD, but have poor response to GH therapy. This case underscores the importance of social environment in the growth of the individual.