Faculty Bibliography

The rates of long-term diabetes related complications have declined substantially over the past decade. On the contrary, the growth in the incidence of prediabetes is note-worthy - especially in the population 60 years and above. As a result, the focus is now shifting toward early identification and prevention of diabetes. Prediabetes is a high risk state in the continuum of glycemic progression and beta cell dysfunction toward the development of diabetes mellitus. Observational studies have shown association of prediabetes with increased incidence of vascular complications. Long-term prospective randomized clinical trials across the globe have demonstrated a reduction in progression of prediabetes when lifestyle modifications are adopted and these effects can last up to 20 years beyond the period of intervention. While there has been recent interest in using pharmacotherapy for diabetes prevention, they have not been shown to be superior to lifestyle changes. This review hopes to provide a concise summary for the interested reader.

A 71-year-old woman with type 2 diabetes mellitus, chronic kidney disease 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. To our knowledge, this is the first reported case of hallucinations associated with the use of an alpha-glucosidase inhibitor and highlights a previously unappreciated risk associated with the use of this generally quite benign drug class.

Background: Interventions that are effective in treating PCOS are often effective in treating CAH. Both Vitamin D replacement and HMGCoA inhibitors (statins) have been reported to be effective in treating PCOS, while we have reported that ergocalciferol is effective in treating patients with both classical and non-classic 11-hydroxylase deficiency. Use of these agents in treating non-classic 21-hydroxylase deficiency has not been previously reported, with the exception of one previous report in 4 women with non-classic 21-hydroylase deficiency treated with simvastatin only. Clinical case: A 56 year old woman presented with complaints of hirsutism, male pattern alopecia, and acne; reproductive history was normal. Physical examination was remarkable for the above as well as for acanthosis nigricans in the axillae, neck, and groin. Investigation revealed a serum 17-OH-progesterone (17OHP) concentration by liquid chromatography/ tandem mass spectrometry (LC/MS/MS) of 46 ng/dl (<45) and a baseline serum 25-OH-Vitamin D (25OHD) concentration by immunoextraction of 15 ng/dl (30-100). LDL cholesterol by calculation was 171.0 mg/dl (<100). Treatment was commenced with ergocalciferol 50,000 IU every 2 weeks and simvastatin 10 mg daily at bedtime. Thirteen months later 17-OHP was 27 ng/dl; 25OHD was 37 ng/dl. LDL fell to 157.4 mg/dl. There were no new acne lesions, alopecia had resolved, and hirsutism had diminished. Conclusion: This is the 5th patient reported whose non-classic 21-hydroxylase deficiency improved with simvastatin and the first patient with this disorder who responded to Vitamin D replacement. Further studies may confirm that this combination is an effective treatment for patients with non-classic 21-hydroxylase deficiency with hypercholesterolemia and Vitamin D deficiency. Our findings are consistent with our earlier reports showing that reduction of insulin levels is associated with improvement in CAH parameters

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.