Faculty Bibliography

Background Several studies confirm higher prevalence of vitamin D insufficiency or deficiency in psychiatric patients. The incidence is highest in schizophrenic patients. However, up to this date, it is not conclusive that vitamin D deficiency is a cause or effect of psychiatric illnesses. In addition to a few commonly known contributing factors for vitamin D deficiency in general population such as inadequate sun exposure and poor nutritional intake, some of anti-psychotic medications are known to interfere with intrinsic vitamin D synthesis. Objective The objective of this study is to identify the prevalence and metabolic association of vitamin D deficiency in urban psychiatric population. Method This is a cross-sectional analysis of 108 psychiatric patients in an urban municipal hospital in Brooklyn, New York. Vitamin D levels were obtained to assess the prevalence of vitamin D deficiency and insufficiency and to examine the association of such deficiency on other metabolic parameters. Result Mean age (+/-SD) was 41.0 (+/-14.2) and mean BMI (+/-SD) was 28.2 (+/- 7.4). Among the entire study population, 70% had vitamin D deficiency (25 OH vitamin D < 20 ng/ml) and 99% had vitamin D insufficiency (25 OH vitamin D < 30 ng/ml). There was no significant difference in age, gender, BMI, blood pressure, HbA1c, fasting blood glucose, creatinine, calcium, and TSH in patients with vitamin D deficiency when compared to patients with normal vitamin D values. Conclusion Vitamin D deficiency is highly prevalent in urban psychiatry population. Implications of such deficiency on clinical metabolic parameters are largely unclear

Congenital adrenal hyperplasia (CAH) is a well-characterised family of disorders of the adrenal cortices, resulting in varying degrees of cortisol, aldosterone and androgen deficiency or androgen excess, depending on the enzyme(s) affected and the degree of quantitative or functional enzyme deficit. Withania somnifera (WS), commonly known as Ashwagandha, is a medicinal plant that has been employed for centuries in ayurvedic medicine. Preclinical studies have shown that WS increases circulating cortisol levels and improves insulin sensitivity. We report the case of a 57-year-old woman with non-classical adrenal hyperplasia due to both 3-beta-ol dehydrogenase deficiency and aldosterone synthase deficiency who was self-treated with WS for 6 months. After 6 months of treatment her serum 18-OH-hydroxycorticoserone, 17-OH-pregnenolone, corticosterone and 11-deoxycortisol decreased by 31%, 66%, 69% and 55%, respectively. The biochemical improvement was accompanied by a noticeable reduction in scalp hair loss.

A 37-year-old woman presented with a history of reactive hypoglycaemia, non-classic adrenal hyperplasia (NCAH), osteopenia and fibromyalgia. After several months of palpitations, postural orthostatic tachycardia syndrome (POTS) was diagnosed by tilt table studies. Her heart rate (HR) reached 191 bpm at 60 degrees from horizontal. Investigation suggested increase in epinephrine and norepinephrine levels in response to tilt table. Her 25(OH) vitamin D level measured by immunoextraction radioimmunoassay was 35 pg/ ml (normal 9-54 pg/ml) while her 1,25(OH)(2) vitamin D3 level was 24 pg/ml (normal 30-67 pg/ml). Accordingly, she was started on calcitriol 0.25 mcg orally daily. At her next visit after 5 months, she reported remarkable improvement in her palpitations and had been working full time for the past 4 months. HR both seated and upright was 72 bpm. After 3 months, her 1,25(OH)(2) vitamin D3 level on calcitriol was 40 pg/ml. The authors suggest that 1-alpha hydroxylation defects should be sought and treated, if present, with calcitriol in patients with POTS.

The authors report a patient whose polycystic ovarian syndrome (PCOS) and increased calcitriol level were associated with neurocysticercosis (NCC), for which she refused standard therapy. Based upon a report on treatment with tamoxifen in murine cysticercosis,1 she was offered raloxifene. She began raloxifene 60 mg/day on 21 January 2010. On 17 March 2010 she was pregnant, and was terminated on 14 April 2010. MRI 26 April 2010 showed diminution in size, shrinkage and loss of viability in a number of the cysts. Total lesions fell from 37 to 33, 10 lesions shrunk, 5 resolved, 18 were unchanged, 4 enlarged and 1 new lesion developed. Concomitantly serum calcitriol fell from 81 to 41 pg/ml while 25-OH-vitamin D level fell from 34 to 30 ng/ml. Alteration of the hormonal milieu may reduce cestode burden in human NCC. The pregnancy on raloxifene, though unfortunate, supports the concept that NCC caused the PCOS. Serum calcitriol may be a useful biomarker for assessing disease activity in NCC.

A 71 year old woman with Type 2 diabetes mellitus (Type 2DM), chronic kidney disease stage IV (CKD stage IV), primary hypothyroidism, and osteoarthritis whose prescribed treatment included miglitol 50 mg thrice daily with the first bite of meals reported that she suffered visual hallucinations while taking miglitol, which resolved within a few days of stopping the drug. When she resumed miglitol hallucinations recurred within a few days and again resolved within a few days of stopping the drug. At no point were hallucinations associated with any symptom of hypoglycemia or a low finger stick glucose reading. Glycemic control was suboptimal with HbA1c by HPLC = 11.2%. She was still hypothyroid on thyroxine replacement with TSH by chemiluminescence = 39.7 mIU/ml.Although, in general, miglitol is minimally absorbed following oral administration (2-3%) it is mostly eliminated unchanged via the renal route and thus, may accumulate, in the setting of renal failure. Likewise, incompletely compensated hypothyroidism may result in drug accumulation. Once absorbed, miglitol is able to cross the blood/brain barrier and potentially inhibit the alpha-glucosidase enzymes of the the central nervous system (CNS), eg isomaltase, resulting in CNS glycogen accumulation mimicking genetic glycogen storage diseases, eg Pompe disease, which may also present with hallucinations. Inhibition of CNS alpha-glucosidases may also result in formation of aneurysms. Although one series has reported a 2% incidence of hallucinations in patients taking the related drug, acarbose, the risk is not widely appreciated and it is not a reported adverse effect in the package insert for either medication.We conclude that alpha-glucosidase inhibitors should be used with caution in patients with coexisting renal insufficiency and incompletely treated hypothyroidism. CNS changes, in the absence of hypoglycemia should dictate drug discontinuation

Although neuropathy affects one-fifth of diabetics, recurrent episodic concomitant attacks of gastroparesis and sixth nerve palsy are rare.Our patient, a 57 year old woman, had three distinct instances when she had simultaneous presentations of gastroparesis presenting with early satiety, frequent eructation, acid reflux, nausea and vomiting, as well as diplopia due to right sixth cranial nerve palsy. She had a history of type 1 Diabetes Mellitus (DM) for 45 years and been on insulin since diagnosis but her glucose control initially had been suboptimal. The diagnosis of gastroparesis was confirmed on the first presentation with single isotope nuclear gastric emptying time with administration of 99Tc sulfur colloid with a scrambled egg test meal for solids. T1/2 for solids was prolonged at >150 min (normal:90-120 min). The initial impression of mononeuritis as the cause of her 6th nerve palsy was confirmed by the neuro-opthalmologist. Her symptoms resolved with the control of blood glucose, use of glucocorticoids and topical clonidine which has been proved useful in the treatment of diabetic gastroparesis and enteropathy.Our patient is unique in that she has had 3 distinct simultaneous occurences of diabetic gastroparesis and mononeuritis with 6th nerve palsy during the course of her illness. Good control of blood glucose and use of steroids and topical clonidine is useful in the management of such attacks

Both thiazolidinediones, rosiglitazone and pioglitazone have been associated with a small, but significantly increased risk of bladder carcinoma. Recently, metformin use has been associated with a decreased risk of a variety of cancers.Our patient, a 61 year old male, with Type 2 diabetes, metabolic syndrome, coronary artery disease, cerebrovascular disease, and peripheral arterial disease had been taking a combination of 4 mg rosiglitazone/1000 mg metformin twice daily for >= 5 years. On 01/22/2010 this combination was replaced with pioglitazone 45 mg daily plus metformin 1000 mg twice daily to improve his lipid profile. In 02/2010, the patient, who was taking enteric coated aspirin 81 mg and clopidogrel 75 mg daily following stent placement, presented with painless gross hematuria. Rectal examination and PSA by chemiluminescence were normal. Urine culture and cystoscopy were negative. Pelvic CT with contrast revealed possible mild thickening of the anterior bladder wall, possibly artifactual due to poor bladder distention. The Vysis UroVysion Bladder Cancer assay was performed on the patient's voided urine on 02-18-2010 by fluorescence in situ hybridization (FISH), which revealed 26 cells that were tetraploid or nearly tetraploid for chromosomes 2,7,17, and the 9p21 locus (normal <10). This finding is consistent with either bladder carcinoma or "umbrella" cells-cells in the G2 phase of the cell cycle. A second FISH assay revealed similar findings. Pioglitazone was stopped on 03/03/2010. Follow-up cystoscopies remained negative. Repeat FISH assay performed on 09/08/2010 was normal.We conclude that: 1) pre-cancerous/early cancerous changes in bladder epithelial cells associated with thiazolidinedione (TZD) use, in the absence of microscopic tumor, may be reversible when the TZD is stopped; 2) metformin may play an as yet undefined role in delaying formation of macroscopic bladder tumors and/or in reversing abnormal bladder cytology via the activation of AMP kinase and inhibition mTOR signaling

Objective: To present a rare case of otherwise asymptomatic hypothyroidism presenting with hypertensive emergency and pericardial tamponade.Patient, Methods and Case Report:A 39 yo female presented to the Emergency Department (ED) complaining of chest pain, myalgia, decreased baseline tolerance, and swelling of the lower extremities. In the ED, her blood pressure (BP) was 202/117 mm Hg; apical heart rate was 75 bpm. On auscultation, distant, muffled heart sounds were heard, without murmur or gallop; no other features of hypothyroidism were noted. On palpation, a normally sized thyroid gland without palpable nodules was noted. ECG showed diffuse T wave flattening in the anterolateral leads. Shortly after admission, she developed increasing respiratory distress and required intubation. Her BP dropped to 80 mm Hg after intubation. Bedside echocardiogram was consistent with cardiac tamponade and diastolic collapse of right atrium and ventricle. Surgery was consulted and immediate pericardiocentesis was done. Analysis of pericardial fluid and other laboratory data ruled out all common causes except for hypothyroidism as a cause of cardiac tamponade. Serum TSH by chemiluminescence was 75.32 mIU/L (0.40-5.50), total serum cholesterol was 280 mg/dl, LDL calculated was 197 mg/dl.Discussion:Only a very few cases have been reported with hypertension as part of the presentation of cardiac tamponade in myxedema patients. This is a unique presentation in a patient who was generally asymptomatic with regard to hypothyroid patient. In hypothyroid patients, normal BP is maintained due to slow progression of pericardial distension allowing compensatory mechanisms to be activated. In our patient the BP remained elevated after pericardiocentesis. Possible mechanisms for hypertension could be increased serum catecholamine levels, enhanced nonadrenergic reactivity of vascular smooth muscle, and an increase in binding the alpha-1 adrenergic receptor as described by Brown et al (1). Conclusion s:- In patients presenting with hypertensive emergencies and cardiac tamponade, it is crucial to check the thyroid function tests though the patient may not have any other signs or symptoms of hypothyroidism.- Proper diagnosis and timely thyroid hormone replacement will improve the prognosis in such patients

BackgroundVitamin D Deficiency/Insufficiency (VDDI) has become common worldwide in association with lifestyle changes and increased surveillance. Although its role in regulating calcium and phosphorus homeostasis is well recognized, recent studies have identified a relationship between low vitamin D levels and multiple medical conditions. VDDI is also reported in association with Type II DM, insulin resistance (IR), and polycystic ovarian syndrome (PCOS). Non-classic adrenal hyperplasia (NCAH) shares many features with PCOS including: IR, hyperandrogenism, menstrual irregularity, polycystic ovaries, and hypofertility. Many of the same insulin-sensitizing interventions that ameliorate PCOS also ameliorate the biochemical and clinical expression of NCAH including: metformin, thiazolidinediones, weight loss, and Roux-en-Y gastric bypass. Vitamin D has been shown to improve the ovulation rate of patients with PCOS. Therefore, it would not be surprising if VDDI was prevalent in NCAH patients and if Vitamin D supplementation ameliorated the expression of NCAH. Methods and ResultsWe reviewed the charts of 9 NCAH patients; 6 women and 3 men, aged 28 to 71 years old, all with concomitant VDDI. 25-OH-Vitamin D was measured by liquid chromatography tandem mass spectrometry (LCMSMS). Serum 25-OH-Vitamin D levels < 20 ng/dl were considered deficient and levels between 20 and 30 ng/dl were considered insufficient. Vitamin D supplementation was initiated in all nine patients.One patient, a 71 year old woman with a baseline serum 11-deoxycortisol measured by LCMSMS of 63 ng/dl (normal: <37) and a baseline 25-OH-Vitamin D level of 29 ng/dl was treated with ergocalciferol 50,000 IU every 2 weeks. Treatment was accompanied by a fall in serum 11-deoxycortisol to < 20 ng/dl. Conclusion sFrom our observation in this series of patients, we believe that VDDI may be more prevalent in NCAH patients than in the general adult population and based on the many clinical similarities between this condition and PCOS, Vitamin D may be an effective component of NCAH treatment. The decrease in 11-deoxycortisol levels observed in one of our patients following supplementation with vitamin D potentially offers an anecdotal occurrence of improvement of the primary condition (NCAH) which merits further analysis. Accumulated evidence from larger randomized clinical trials will be needed to confirm the therapeutic value of vitamin D supplementation for the general population of patients with NCAH

Withania somnifera, commonly known as ashwagandha, is a traditional Aryuvedic medicinal plant reported to be beneficial for a variety of medical conditions owing to its antioxidant, anti-inflammatory, immune-modulating, and antistress properties. Anwer et al (2008) have also shown that Withania somnifera (WS) increases insulin sensitivity in rats. Non-classical adrenal hyperplasia (NCAH) has been shown to be associated with insulin resistance (IR) and interventions which reduce IR, including metformin, thiazolidinediones, and weight loss ameliorate NCAH. Consequently, we hypothesized that WS could be beneficial in a patient with a non-classical adrenal hyperplasia.In this case report, a 57-year-old female with non-classical congenital adrenal hyperplasia due to both 3-beta-ol dehydrogenase deficiency and aldosterone synthase deficiency took 400 mg WS orally twice daily for 6 months. Following this treatment there was a 31% reduction in 18-hydroxycorticosterone by mass spectrometry from 55 to 38 ng/dL (9-58), a 66% reduction in 17-hydroxypregnenolone by HPLC/mass spectrometry from 460 to 155 ng/dL (53-357), a 69% reduction in corticosterone by liquid chromatography/tandem mass spectrometry from 2416 to 748 ng/dL (130-820), and a 55% reduction in 11-deoxycortisol by liquid chromatography, tandem mass spectrometry from 89 to 40 ng/dL (12-158). The biochemical improvement was accompanied by a reduction in the amount of scalp hair loss.We conclude that ashwagandha root could be used as a novel natural remedy for congenital adrenal hyperplasia if double blind, randomized control trials confirm our findings