METHODS: We describe the clinical presentation, diagnostic work-up, management, and clinical course of a patient admitted with SMA syndrome who was subsequently found to have a hypothalamic germinoma.
RESULTS: An adolescent boy was admitted to the surgical ward with progressive weight loss over a 2 year period and postprandial vomiting. He was diagnosed with SMA syndrome based on evidence of proximal duodenal dilatation, extrinsic compression of the distal duodenum, and a narrowed aortomesenteric angle (16°). Investigations performed to exclude thyrotoxicosis unexpectedly revealed secondary hypothyroidism and further evaluation demonstrated evidence of pan-hypopituitarism. Psychiatric evaluation excluded anorexia nervosa and bulimia. Magnetic resonance imaging (MRI) of the brain revealed a heterogeneously enhancing hypothalamic lesion, but a normal pituitary gland. Hormone replacement with hydrocortisone, desmopressin, testosterone, and thyroxine resulted in weight gain and resolution of gastrointestinal symptoms. A transventricular endoscopic biopsy subsequently confirmed a hypothalamic germinoma and he was referred to an oncologist.
CONCLUSION: SMA syndrome secondary to severe weight loss is an uncommon cause of upper gastrointestinal obstruction. While there have been reports of poorly controlled diabetes mellitus and thyrotoxicosis manifesting as SMA syndrome, there are no published reports to date of SMA syndrome secondary to hypothalamic/pituitary disease. Management of SMA syndrome is conservative, as symptoms of intestinal obstruction resolve with weight gain following treatment of the underlying cause. Awareness of this uncommon presentation of endocrine cachexia/hypothalamic disease will prevent unnecessary laparotomies and a misdiagnosis of an eating disorder.
METHODS: We studied 50 patients (31 males) with mean age 57 ± 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function.
RESULTS: Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes, 18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively. Hyperprolactinaemia was present in 30% of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01.
CONCLUSION: Despite low awareness and detection rates, HP dysfunction post-NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors.
PATIENTS & METHODS: DPP4, WFS1 and KCNJ11 gene polymorphisms were genotyped in a cohort study of 662 T2DM patients treated with DPP-4 inhibitors sitagliptin, vildagliptin or linagliptin. Genotyping was performed by Applied Biosystems TaqMan SNP genotyping assay.
RESULTS: Patients with triglyceride levels less than 1.7 mmol/l (odds ratio [OR]: 2.2.; 95% CI: 1.031-4.723), diastolic blood pressure (DBP) less than 90 mmHg (OR: 1.7; 95% CI: 1.009-2.892) and KCNJ11 rs2285676 (genotype CC) (OR: 2.0; 95% CI: 1.025-3.767) were more likely to response to DPP-4 inhibitor treatment compared with other patients, as measured by HbA1c levels.
CONCLUSION: Triglycerides, DBP and KCNJ11 rs2285676 are predictors of the DPP-4 inhibitor treatment response in T2DM patients.