Faculty Bibliography

Background: Hyperammonemia is a prognostic factor in ornithine transcarbamylase deficiency (OTCD), often resulting in severe and long term neurological impairment. Biotin deficiency has been shown to cause hyperammonemia (OTCD) in rats and yeast. We present a case of misdiagnosed OTCD with amelioration in ammonia levels and neuropsychiatric condition following biotin supplementation. Clinical case: Our patient is a 48 year old man with a long history of psychiatric disorder who was brought in by ambulance to the emergency department from a nursing home on account of altered mental status, resulting in abusive behavior and visual hallucinations. Physical examination showed mild icterus, and impaired vision. He was being managed for dementia, seizure disorder, bipolar disorder, schizoaffective disorder and catatonia. He also has benign prostatic hypertrophy, T2DM, and hypertension on treatment. Further investigation revealed hyperammonemia by spectrophotometry (120mg/dl, reference range 12 - 47mg/dl) with normal routine liver function tests, raising the suspicion of a urea cycle disorder. Allopurinol challenge test was positive. Treatment was instituted with low protein diet, l-arginine, citrulline, lactulose, rifaximin and the nitrogen scavenger, sodium phenylacetate. However, his plasma ammonia level fluctuated between 120mg/dl and 226mg/dl. Biotin 800 mcg daily was introduced, which was associated with a fall in the level of ammonia to 69mg/dl with a remarkable improvement of the patient's neuropsychiatric condition. Subsequently, the patient was discharged to a rehabilitation center. Conclusions: OTCD is a rare inborn error of metabolism of the urea cycle. Improper diagnosis can result in late presentation cum long term neuropsychiatric sequelae. Biotin therapy may be effective in reducing hyperammonemia while improving neuropsychiatric derangement. This is the first reported use of biotin supplementation in human OTCD. Randomized clinical trials are needed to confirm the effects of biotin in OTCD

Background: We have previously reported that the Ayruvedic herb, Ashwagandha (Withania somnifera) (WS), which is known to be an insulin sensitizer, is effective in treating both non-classic 3-beta-ol-dehydrogenase deficiency, and non-classic aldosterone synthase deficiency. Here we report the effects of its use in a patient with non-classic 11-hydroxylase deficiency. Clinical Case: A 78-year old woman with a history of hypothyroidism, hypertension and stage III chronic kidney disease presented complaining of acne and alopecia. Investigation revealed a serum 11-deoxycortisol concentration by liquid chromatography/tandem mass spectrometry of 91ng/dl (<37) on 6/18/2013. Treatment was initiated with a standardized preparation of Ashwagandha root at a dosage of 400 mg twice daily. Repeat serum 11-deoxycortisol concentration on 4/9/2014 was 64ng/dl. The Ashwagandha dose has been raised to 400 mg in the morning and 800 mg in the evening. Biochemical improvement has been accompanied by improvement in acne and hair loss. Conclusions: Ashwagandha root may be effective in treating some patients with non-classic 11-hydroxylase deficiency, as it is in some patients with non-classic aldosterone synthase deficiency and non-classic 3-beta-ol-dehydrogenase deficiency. Reduction in insulin resistance/hyperinsulinemia is likely to be one the underlying mechanisms of this observed treatment effect

Background: We have previously reported that weight loss (WL) resulted in amelioration of non-classic aldosterone synthase deficiency and that vitamin D replacement in patients with both classic and non-classic 11-hydroxylase deficiency, who were vitamin D deficient/insufficient, normalized their biochemical profiles. Clinical Case: A 44 year old woman presented with chief complaints of infertility, irregular menses, and male pattern scalp hair loss. Investigation revealed a serum 11- deoxycortisol concentration by RIA after extraction and chromatography of 68 ng/dl (<62), which suppressed to reference range after 1 mg dexamethasone. Serum 25-OH-vitamin D (25OHD) by immunoextraction was 14 ng/dl (30-100). She weighed 63.5 kg and her BMI was 22.5 kg/m². Treatment was commenced with ergocalciferol 50,000 IU weekly and the patient was prescribed metformin 500 mg daily after supper, but she never took the latter. When she returned 7 months later her weight had fallen to 61.2 kg, BMI to 21.68 kg/m², and her serum 11-deoxycortisol to 19 ng/dl; serum 25OHD had risen to 28 ng/dl. Her male pattern hair loss had resolved and her menses were normalized. Conclusions: Weight loss may be effective in treating non-classic 11-hydroxylase deficiency as it is in non-classic aldosterone synthase deficiency by improving insulin resistance (hyperinsulinemia). Ergocalciferol may work by the same mechanism and in addition, the presence of vitamin D receptors in the adrenal cortex suggests the possibility of a direct effect of vitamin D on adrenal steroidogenesis

Background: Secondary pulmonary hypertension is a known complication of hyperthyroidism, and it can lead to dilatation of the right atrium and ventricle and ultimately to right-sided heart failure. It has also been shown that in an individual with patent foramen ovale (PFO), right-to-left intracardiac shunt can be observed in the presence of elevated right atrial pressure. Case Report: Here we report a case in which we observed resolution of right-to-left shunt through PFO with treatment of hyperthyroidism in a 41-year-old Scandinavian female who was newly diagnosed with Grave's disease, presenting with dyspnea at rest, palpitations, diaphoresis, tremor, and photophobia. She was noted to have chemosis, stare, and thyroid bruit. Serum TSH by chemiluminescence was 0.013 (0.4-5.5) mIU/L, total T4 by chemiluminescence was >30.0 (4.5-12.0) mcg/dl, T3RU by spectrophotometry was 53.89 (22.50-37.0) %, total T3 by immunoassay was >800 (60.0-181.0) ng/dl. TSIG by bioassay was 500 (<140) % Baseline. Baseline transthoracic echocardiogram (TTE) at the initial presentation revealed severe tricuspid regurgitation, pulmonary arterial pressure of 60mmHg, and atrial septal defect (ASD) of secundum/PFO type with right-to-left shunt. The patient was started on methimazole 10 mg daily for treatment of Grave's disease. Approximately 8 weeks after the initial TTE, repeat study was performed, which demonstrated only mild pulmonary arterial hypertension and no evidence of the previously demonstrated ASD. Conclusions: We postulate that the severe pulmonary hypertension leads to an elevated right atrial pressure, and recurrence of a pre-existing PFO served as a conduit for the right-to-left intracardiac shunt. With the aforementioned treatment of Graves's disease, this right-sided hypertension improved, leading to resolution of the PFO. This is the first reported case of resolution of PFO with improvement of hyperthyroidism

The increasing prevalence of diabetes especially type 2 diabetes worldwide is indisputable. Diabetics suffer increased morbidity and mortality, compared to their non-diabetic counterparts, not only because of vascular complications, but also because of an increased fracture incidence. Both types 1 and 2 diabetes and some medications used to treat it are associated with osteoporotic fractures. The responsible mechanisms remain incompletely elucidated. In this review, we evaluate the role of glycemic control in bone health, and the effect of anti-diabetic medications such as thiazolidinediones, sulfonylureas, DPP-4 inhibitors, and GLP-1 agonists. In addition, we examine the possible role of insulin and metformin as anabolic agents for bone. Lastly, we identify the current and future screening tools that help evaluate bone health in diabetics and their limitations. In this way we can offer individualized treatment, to the at-risk diabetic population.

Non-classic adrenal hyperplasia (NCAH) has been associated with insulin resistance (IR). Therapies such as metformin, thiazolidinediones and lifestyle alterations improve IR and also ameliorate the biochemical and clinical abnormalities of NCAH, much as they do in polycystic ovarian syndrome (PCOS). More recently, bariatric surgery, such as Roux-en-Y gastric bypass (RYGBP), has also been associated with improvement in IR and amelioration of PCOS and may, therefore, be beneficial in NCAH. We report a case of a 39-year-old, deaf-mute, obese woman with NCAH due to 11-hydroxylase deficiency who underwent RYGBP followed by improvement of NCAH manifestations. She was initially treated with metformin and pioglitazone, which lowered serum 11-deoxycortisol from 198 ng/dl (<51) to 26 ng/dl. Five weeks after undergoing RYGBP her body mass index fell from 44.18 kg/m(2) to 39.54 kg/m(2) and, despite not taking metformin or pioglitazone, serum 11-deoxycortisol remained normal at <40 ng/dl. Concurrently and subsequently, her NCAH symptoms, for example, alopecia, hirsutism and irregular menses normalised as well. We conclude that RYGBP, like other interventions that reduce IR, may be another way of treating non-classic 11-hydroxylase deficiency in selected patients.

A 28 year old male with a history of cogenital panhypopituitarism ( not currently on any hormonal replacement), and who is an ex- alcohol abuser presented to the Emergency Department complaining of hematemesis x 1 day associated with lightheadedness and weakness. Stool and nasogastric lavage were positive for occult blood. On upper GI endoscopy the patient was found to have multiple varices on the distal esophagus and stomach fundus. Immediate banding was done to control bleeding and patient was transferred to ICU. In ICU, EKG showed 3rd degree complete heart block ( previous EKGs are unavailable). A pacemaker was placed. CT abdomen showed nodular liver contour compatible with cirrhosis, and a markedly enlarged spleen. Further work up for panhypopituitarism yielded the following results: FSH by chemiluminescence=0.94 mIU/L (1.6-8.0), LH by chemiluminescence<0.07 mIU/L (1.5-9.3), TSH by chemiluminescence 0.21 mIU/L (0.4-4.5), ACTH by chemiluminescence 52 pg/ml (6-50), Total Testosterone by liquid chromatography tandem mass spectrometry (LCMS/MS) 9 ng/dl (250-1100)', IGF-1 by liquid chromatography mass spectrometry LC/MS 33 ng/ml (114-492) which is suggestive of partial hypopituitarism. Discussion: The mechanism of liver injury in congenital hypopituitarism is still unknown. It is hypothesized that cortisol and/or growth hormone deficiency both play a role in delayed maturation of bile acid synthesis and transport, and this leads to cholestasis in infancy. The liver disease often resolves following endocrine replacement therapy, and the cholestasis resolves within 6 weeks of starting treatment with thyroxine, cortisol and GH. However, delay in diagnosis and treatment of the endocrinopathy may lead to persistently abnormal liver function tests, and in some cases to irreversible liver cirrhosis / portal hypertension. In our case patient did not take hormonal therapy and might have developed portal hypertension leading to esophageal varices and bleeding. It is likely that his former ethanol abuse contributed to his liver disease. Complete heart block occurs in hypothyroidism and is reported to be reversible with l-thyroxine replacement. Conclusion: Untreated congenital hypopituitarism can present with heart block and portal hypertension with bleeding. Clinicians should be aware of associated complications and start hormonal therapy early

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.